summary 2023 02 23 24 508

MEETING OF THE ADVISORY
COMMITTEE ON IMMUNIZATION
PRACTICES (ACIP)
FEBRUARY 22 -24, 2023
MEETING SUMMARY
CONTENTS
WEDNESDAY: FEBRUARY 22, 2023 .......................................................................................................... 5
WELCOME AND INTRODUCTIONS ...................................................................................... 5
Call to Order/Roll Call ......................................................................................................... 5
Announcements .................................................................................................................. 5
MPOX VACCINE .................................................................................................................... 6
Opening Remarks ............................................................................................................... 6
Session Introduction ........................................................................................................... 6
Epidemiology of Mpox During the Current 2022 Outbreak in the United States ................... 8
JYNNEOS Vaccine Effectiveness ......................................................................................11
JYNNEOS Vaccine Safety ................................................................................................. 13
Mpox Vaccine Acceptability and Uptake from Cross -Sectional Surveys .............................17
Interim Clinical Considerations ...........................................................................................20
EtR: Use of JYNNEOS During Mpox Outbreaks ................................................................. 22
ACIP Discussion Points, Observations, Suggestions on Mpox Vaccine .............................27
Vote: Mpox Vaccine ...........................................................................................................31
RESPIRATORY DISEASE SURGE, FALL 2022, UNITED STATES ......................................31
Discussion Points ...............................................................................................................33
INFLUENZA VACCINE ..........................................................................................................35
Introduction ........................................................................................................................35
US Influenza Activity Update ..............................................................................................35
Preliminary 2022 -2023 Influenza Vaccine Effectiveness: CDC Networks ...........................36
Preliminary 2022 -2023 Influenza Vaccine Effectiveness: Wisconsin ..................................38
Update on Published Estimates of LAIV4 Effectiveness: Background ................................39
ACIP Discussion Points, Observations, Suggestions on Influenza Vaccine ........................40

   PNEUMOCOCCAL VACCINES .............................................................................................42
Introduction ........................................................................................................................42
Epidemiology of Pneumococcal Disease among US Children ............................................43
Estimating the Impact of Higher -Valency PCVs on Pediatric Outpatient ARI Visits and
Antibiotic Use .....................................................................................................................46
PCV20 Phase 2/3 Study Results among Children ..............................................................49
Preliminary EtR/GRADE for PCV20 use in US Children .....................................................51
Pneumococcal Vaccines WG Considerations and Next Steps ...........................................55
Merck Comments ...............................................................................................................56
ACIP Discussion Points, Observations, Suggestions on Pneumococcal Vaccine ...............57
PUBLIC COMMENTS ............................................................................................................59
THURSDAY: FEBRUARY 23, 2023 ............................................................................................................ 62
AGENCY UPDATES ..............................................................................................................62
Centers for Disease Control and Prevention ......................................................................62
Centers for Medicare and Medicaid Services .....................................................................63
Health Resources and Services Administration ..................................................................64
Indian Health Service .........................................................................................................64
National Institutes of Health ...............................................................................................65
Office of Infectious Disease and HIV/AIDS Policy ..............................................................65
MENINGOCOCCAL VACCINES ............................................................................................ 66
Introduction ........................................................................................................................66
Epidemiology of Meningococcal Disease in the United States ...........................................66
Pfizer Pentavalent Meningococcal Vaccine ........................................................................68
Workgroup Considerations ................................................................................................. 71
ACIP Discussion Points, Observations, Suggestions on Meningococcal Vaccines .............73
POLIO VACCINES ................................................................................................................75
Introduction ........................................................................................................................75
Recommendations for Adult Polio Vaccination ................................................................... 75
ACIP Discussion Points, Observations, Suggestions on Polio Vaccines ............................80
RSV VACCINES: PEDIATRIC/MATERNAL ...........................................................................80
Introduction ........................................................................................................................80
Cost-Effectiveness  Analysis for Nirsevimab: CDC Model ...................................................81
Cost-Effectiveness  Analysis for Nirsevimab: Comparison to Manufacturer Model ..............85
EtR Framework for Nirsevimab ..........................................................................................89
Clinical Considerations for Nirsevimab ...............................................................................97
Safety and Efficacy of RSV Bivalent Prefusion F (PreF) Maternal Vaccine ........................98
Workgroup Considerations ............................................................................................... 103
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    ........................................................................................................................................ 103 ACIP Discussion Points, Observations, Suggestions on Pediatric/Maternal RSV Vaccines
RSV VACCINES: ADULT .................................................................................................... 107
Introduction ...................................................................................................................... 107
Cost-Effectiveness  of the GSK and Pfizer Vaccines: Main CDC Model ............................108
Comparison of Cost -Effectiveness Results of the Main CDC Model and Each Manufacturer
Model (GSK & Pfizer) ....................................................................................................... 111
EtR/GRADE for 2 Vaccines (GSK & Pfizer) ...................................................................... 115
GSK Statement ................................................................................................................ 123
Pfizer Statement .............................................................................................................. 124
ACIP Discussion Points, Observations, Suggestions on Adult RSV Vaccines .................. 124
CHIKUNGUNYA VACCINE .................................................................................................. 126
Introduction ...................................................................................................................... 126
Global Epidemiology of Chikungunya ............................................................................... 127
Chikungunya in US Travelers ........................................................................................... 129
Persistent Arthralgia Following Chikungunya ................................................................... 131
Workgroup Considerations ............................................................................................... 134
ACIP Discussion Points, Observations, Suggestions on Chikungunya Vaccines .............. 134
DENGUE VACCINE ............................................................................................................. 135
Introduction ...................................................................................................................... 135
Takeda Dengue Vaccine (TAK- 003) Safety and Efficacy ................................................. 136
Workgroup Considerations ............................................................................................... 139
ACIP Discussion Points, Observations, Suggestions on Dengue Vaccines ...................... 141
VARICELLA ......................................................................................................................... 141
Public Health Impact of 25 Years of Varicella Vaccination in the United States ................ 141
ACIP Discussion Points, Observations, Suggestions on Varicella Vaccines ..................... 144
FRIDAY: FEBRUARY 24, 2023 ................................................................................................................ 144
COVID -19 VACCINES ......................................................................................................... 144
Introduction ...................................................................................................................... 144
Plan to End the COVID -19 Public Health Emergency (PHE) on May 11, 2023 ................. 145
COVID -19 Vaccine Safety Updates: CDC ........................................................................ 146
COVID -19 Vaccine Safety Updates: FDA ......................................................................... 151
VaST Summary ................................................................................................................ 154
WG In terpretation and Summary ...................................................................................... 155
Updates on COVID -19 Hospitalizations: COVID -NET ...................................................... 157
Updates to COVID -19 Vaccine Effectiveness in the United States ................................... 159
Considerations for Transitioning to Bivalent Primary Series ............................................. 163
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  NCIRD Director Remarks ................................................................................................. 168
Benefit -Risk for COVID- 19 Vaccines ................................................................................ 168
COVID -19 Vaccines: Future Directions ............................................................................ 172
ACIP Discussion Points, Observations, Suggestions on COVID -19 Vaccines .................. 177
CERTIFICATION ....................................................................................................................................... 185
ACIP MEMBERSHIP ROSTER ................................................................................................................ 186
ACRONYMS USED IN THIS DOCUMENT ............................................................................................... 195
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  WEDNESDAY : FEBRUARY 22,  2023
WELCOME AND INTRODUCTIONS
Call to Order/Roll Call
Dr. Grace Lee (ACIP Chair) called to order and presided over the February 22- 24, 2023
Advisory Committee on Immunization Practices (ACIP ) meeting. Dr. Lee conducted a roll call
each day, which established that a quorum was present. A list of Members, Ex Officios , and
Liaison Representatives is included in the appendixes at the end of this summary document.
The following conflict s of interest (COIs) were identified :
Dr. Camile Kotton is involved in a clinical trial for Takeda for an investigational antiviral for
cytomegalovirus (CMV) but is not involved in any of their vaccine projects .
Announcements
Dr. Melinda Wharton (ACIP Executive Secretary, CDC) noted that copies of the slides for the
meeting were available on the ACIP website and were made available through a ShareLink ™
file for ACIP Voting, Ex O fficios , and Liaisons Members . The ACIP is, at its heart, a public body.
Engagement with the public and transparency in all of its processes are vital to the committee’s
work. She indicated that there would be 1 oral public comment session during this meet ing,
which was scheduled for 2:00 PM Eastern Time ( ET) on February 22, 2023. To create a fair and
more efficient process, individuals interested in making an oral comment were asked to submit a request online in advance of the meeting. Priority is given to these advance requests. If more
people make requests than can be accommodated, a blind lottery is conducted to determine who the speakers will be. Speakers selected in the lottery for this meeting were notified in advance of the meeting. Members of the public also may submit written comments via
https://www.regulations.gov using Docket Number ID CDC- 2023-00 07. Information on the
written public comment process, including information on how to mak e a comment, can be
found on the ACIP website.
As noted in the ACIP Policies and Procedures manual, ACIP members agree to forgo
participation in certain activities related to vaccines during their tenure on the committee. For
certain other interests that potentially enhance a member’s expertise while serving on the
committee , CDC may issue limited COI waivers. Members who conduct vaccine clinical trials or
serve on data safety monitoring board s (DSMB s) may present to the committee on matters
related to those vaccines, but those members are prohibited from participating in committee
votes on issues related to those vaccines. Regarding other vaccines of the concerned company,
a member may participate in discussions with the provision that he/she abstains on all votes
related to that company. ACIP members state any COIs at the beginning of each meeting.
5

  MPOX VACCINE
Opening Remarks
Dr. Melinda Wharton (ACIP Executive Secretary, CDC) provided opening remarks for the
Mpox session. She reminded everyone that in November 2021, ACIP unanimously voted in
favor of JYNNEOS as an alternative to the other available vaccine for prevention of Mpox in
persons with certain occupational risk of exposure. During this session, ACIP would be asked to
vote on an additional use of JYNNEOS vaccine for control of Mpox outbreaks. In 2022, a
multinational outbreak of Mpox began with more than 30,000 cases in the United States. In response to this outbreak, J YNNEOS has been successfully used in accordance with
recommendations in CDC’s interim clinical considerations, and there has been a dramatic reduction in case counts. Dr. Wharton emphasized that the vote for use in outbreaks would not
change CDC’s recommendations for use of JYNNEOS in the current outbreak but represents an
update to ACIP’s recommendations that were voted on in late 2021. It is expected that there will
be additional decisions coming to ACIP for a vote in future meetings. The recent outbreak has
highlighted the risks that infectious diseases can present to communities, the importance of a
robust public health response at the state and local level s, the value of engaged partners and
communities in responding to public health threats, and the impact that a vaccine can have in helping to bring an outbreak under control.
Session Introduction
Pablo Sanchez MD (The Ohio State University−Nationwide Children’s Hospital, ACIP
Mpox WG Chair ) introduced the Mpox session. He pointed out that from a historical context,
Mpox is a rare, sometimes life -threatening infection that is endemic in parts of West and Central
Africa. It is caused by the monkeypox virus, which is an orthopoxvirus. There are 2 clades.
Clade 1 was previously known as the Congo Basin Clade, while Clade 2 was previously known
as the West African clade. Mpox can spread from infected animals to people and then person-
to-person from respiratory secretions, skin- to-skin contact with infected body fluids (e.g., fluid
from lesions ), and fomites (e.g., s hared towels, clothing, and bedding).
In terms of the timeline of notable human Mpox events , during 1970 to 2021, Mpox was known
to be endemic in 9 African countries : Cameroon, Central African Republic, Côte d'Ivoire,
Democratic Republic of Congo, Gabon, Liberia, Nigeria, Republic of Congo, and Sierra Leone.
During recent years, there has been a re- emergence of human cases after decades of no
reported cases. The first human case was identified in rural settings in 1970. In 2003, there was
a US outbreak from pet prairie dogs with 47 cases identified. In 2017, there was an outbreak in
Nigeria involving 17 states and 138 cases . In 2018, there were imported cases to the United
Kingdom (UK) and Israel with 3 cases identified. In 2019, there were imported cases to the UK
and Singapore with 2 cases identified. In 2021, there were imported human cases to the UK and
the US with 3 cases identified . A multinational outbreak occurred in 2022.
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   Person- to-person spread has been seen . Historical outbreaks in Africa have been associated
with close skin -to-skin contact and contact with fomites , with zoonotic exposure causing most
cases and a few secondary cases among close contact s. In the US, a 20 03 outbreak resulted in
no secondary cases and no vaccination was offered. In 2021, there were no secondary cases
and ACAM2000 was offered to some contacts.1 In the most recent outbreak in 2022, there were
many secondary cases and over 1 million doses of the JYNNEOS vaccine were administered.
In 2021, ACIP voted for the of orthopoxvirus vaccine, JYNNEOS that was licensed in 2019 , for
pre-exposure vaccination of people at occupational risk for orthopoxvirus exposures. The
JYNNEOS vaccine is a 2-dose series that is administered subcutaneous ly. Recommendations
were published in the Morbidity and Mortality Weekly Report ( MMWR ) on June 3, 2022.2
Currently, there is no ACIP recommendation for the use of JYNNEOS during outbreaks. The
current US national Mpox vaccine strategy is shown in this table:
The US strategy for vaccination with JYNNEOS during the current outbreak has been that the
intradermal route is preferred, but the subcutaneous route can be administered for persons ≥18
years of age or older. The subcutaneous route is recommended for persons <18 years of age .
This is a 2-dose series with a second dose administered 1 month after the first dose.
Regarding the tentative timeline for ACIP discussions and votes, during the February 2023
meeting, the ACIP would be voting on the use of 2-dose JYNNEOS for persons ≥18 years of
age. In June 2023 , ACIP will be discussing the use of 2-dose JYNNEOS for persons aged <18
years of age and would hear updates about vaccine effectiveness (VE) and safety. In October
2023, there will be consideration for a longer -term vaccination strategy for the 2-dose
JYNNEOS vaccine. It is important to note that the current US Mpox vaccination strategy
remains active , which is t hat populations at high risk should continue to be vaccinated.
1 ACAM2000 was offered through a CDC Investigational New Drug Protocol that allows for vaccination after mpox exposure. Only
contacts with highrisk exposures were offered vaccine; none accepted.
2 https://www.cdc.gov/mmwr/volumes/71/wr/mm7122e1.htm
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   This session included updates from the ongoing outbreak in terms of epidemiology , VE, vaccine
safety, community engagement, and equity and implementation; discussion about the use of the
2-dose JYNNEOS subcutaneous ly during Mpox outbreaks with an Evidence- to-
Recommendations Framework presentation and an ACIP vote. Dr. Sanchez presented the
following proposed wording for the vote:
ACIP recommends the 2-dose* JYNNEOS vaccine ser ies for persons aged 18 years and
older at risk of Mpox during an Mpox outbreak. §
*Dose 2 administered one month after dose 1
§ Public health authorities determine whether there is an mpox outbreak; a single case may be considered an mpox outbreak at the discretion of public health authorities. Other circumstances in which a public health response may be
indicated include ongoing risk of introduction of mpox into a community due to disease activity in another geographic area.
Epidemiology of Mpox During the Current 2022 Outbreak in the United States
Sascha Ellington, PhD, MSPH (CDC/NCCDPHP) presented an update on the epidemiology of
the current Mpox outbreak on behalf of the E pidemiology Task Force of CDC ’s Mpox Response.
The first US case associated with the current Mpox outbreak was identified in Massachusetts in
May 2022. Cases initially were associated with travel. Since then, cases have been reported
from all 50 states , DC, and Puerto Rico. More than 30,000 cases have been reported to d ate.
States with the most cases including California, New York, Texas, Florida, Georgia, and Illinois
all reporting more than 1,000 cases. Most cases have occurred in gay, bisexual, and other men
who have sex with men (MSM) . Cases have also been reported in men who have not reported
sex with men, cisgender and transgender women, transgender men, gender diverse people,
children, and teens.
US cases peaked in August 2022 and have declined substantially since. Currently, the 7-day
moving average is 2 cases per day in the US. As of February 8, 2023, 95% of all cases reported
have been amongst cisgender men, 2.9% amongst cisgender women, and a combined 1.7% of
cases have been among transgender men, transgender women, and gender diverse people.
The age of people w ith Mpox ranges from 0, with a few cases reported in neonates , up to 89
years of age. The median age is 34 years. Overall, cases have been reported primarily among
Black, Hispanic, and White persons , with nearly a third in each of these groups. At the start of
the outbreak, about 45% of cases were among White persons, which decreased over time.
Cases in B lack or African American persons increased and cases among Hispanic or Latino
persons have remained fairly stable over the period of the outbreak.
In terms of clinical characteristics and outcomes among cases reported to date, 53% of cases
with available data have been among people living with HIV and 47% of cases have been
among people who are human immunodeficiency virus (HIV)-negative, though only 30% of
cases reported had data on HIV status. Among cases with available data, more than half had
rash reported on the genitals or perianal area, trunk or limbs, head, face, or mouth . About a
quarter had rash on the palms or soles of the feet. About 7.7% of people with Mpox have been
hospitalized and 32 Mpox -associated deaths have been reported, representing 0.1% of cases.
Deaths have occurred primarily in severely immunocompromised persons.
During the current outbreak, Mpox has been spread primarily through sexual or close intimate
contact. Other routes of transmission also have been reported, including household
transmission through injury with a contaminated sharp instrument in a clinical setting, thr ough
piercing and tattooing, and perinatal transmission from an infected mother to an infant around
the time of delivery. Current evidence suggests that some people can spread Mpox virus to
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   others 1 to 4 days before they become symptomatic. However, there is no evidence that people
who never develop symptoms have spread the virus to others. This table summarizes the
specimens in which Mpox has been detected by polymerase chain reaction (PCR) , whether
replication- competent  viruses has been detected, and whether each exposure source has been
associated with transmission:
Replication -competent virus has been detected but isolated in skin lesions, oropharyngeal
swabs, anorectal swabs, semen, urine, and ocular fluid. Mpox has been transmitted from skin-
to-skin contact, oral contact, and from a contaminated sharp. Transmission via exposure to
some sources such as semen can be particularly challenging to assess since exposure typically occurs during close intimate contact that also includes skin- to-skin contact. For this reason,
many exposure sources listed in the table have insufficient data to conclude definitively they are
a source of infection.
As previously mentioned, 95% of cases of Mpox have been reported amongst cisgender men,
and cases have occurred primarily among gay, bisexual, and other MSM . Among the cases
reported in men with data on recent sexual history, 75% reported sexual or close intimate contact with a man in the 3 weeks preceding symptom onset. However, in 25% of cases among
men, no recent male- to-male sexual contact was reported. Over time, the percentage of cases
in men that had recent male- to-male sexual contact has declined from over 80% initially to
about 60%, increases have been observed in the missingness of sexual contact data, which
may contribute at least partially to this decline.
A few specific populations have been less affected overall, but the characteristics of these
cases have contributed to the overall understanding of the epidemiology. Based on dat a from a
publication that was published earlier this year reporting on cases in cisgender women,
3 about
3% of the Mpox cases have been in cisgender women. The m edian age of cases in this group is
32 years, ranging from 15─89 years . Of the cases among cisgender women, 44% were in
Black, non-Hispanic  women ; 25% were in W hite, non- Hispanic women, and 23% were in
Hispanic or Latino women. Of those with available data on HIV status, 8% of cases in cisgender
3 http://dx.doi.org/10.15585/mmwr.mm7201a2
9

   women were HIV -positive, and 92% were HIV negative. While the data were available for only
22% of cases among cisgender women, this is markedly lower than the percent of total cases
that were HIV -positive at 53% and 71% of cases among cisgender women reported a recent
sexual or close intimate part ner.
The same publication also reported on cases in pregnant people. From May 11 ─November 7,
2022, a total of 21 cases of Mpox were reported during pregnancy and 2 cases were reported in
a recently pregnant person, which was defined as within 3 weeks of pregnancy. Among the 12
with exposure data, 9 reported sexual contact and 3 reported household contact to a person
with Mpox. Pregnant people had similar signs and s ymptoms of Mpox as those among non-
pregnant people. Among pregnant people, 4 cases had general lesions during the pregnancy,
but none had lesions at the time of delivery. Tecovirimat was provided to 48% of cases during
pregnancy , with no adverse events (AEs) reported . None of the pregnant cases received post -
exposure prophylaxis (PEP) with JYNNEOS. Outcomes reported to date have included 4
hospitalizations of pregnant people for Mpox indications . All were discharged while still
pregnant. No pregnant cases required intensive care, intubation, or unplanned delivery. To date, pregnancy outcomes have been reported among 3 patients. Of these, 2 were uncomplicated
live births with no transmission to the infant and 1 pregnancy resulted in a first trimester
spontaneous abortion. Two recently pregnant persons experienced symptoms within 3 days of
delivery and their newborns developed lesions within a week. The exact timing of transmission
for these infant cases is unknown.
In another recent report,
4 the characteristics of Mpox cases were assessed among 466
transgender and gender diverse persons. In this analysis, 43% were transgender women, 42%
were gender diverse, and 15% were transgender men. Of the gender diverse persons, 96%
were assigned male sex at birth. The median age of the transgender and gender diverse
persons with Mpox was 32 years and ranged from 18─ 71 years. Among the transgender and
gender diverse persons with Mpox , 28% were Black, 28% were White, and 37% were Hispanic
or Latino. About half of the transgender and gender diverse persons with Mpox were HIV -
positive, which is similar to the percentage observed among all persons with Mpox. Among
transgender and gender diverse persons with Mpox , 84% reported recent sexual or close
intimate partner contact.
In another recent report of 83 cases in children from May 17– September 24, 2022 ,5 there were
16 cases in children aged 0─4 years, 12 cases in children aged 5─12 years , and 55 cases in
children aged 13─ 17 years . Adolescents aged 13 ─17 years were overwhelmingly male and
primarily had sexual exposures, mirroring the epidemiology of cases overall. In younger
children, cases were more evenly divided by sex and were associated with household contact,
frequently from an infected caregiver. While these findings are from a report analyzing data
through September, investigation has continued in cases among children, particularly younger
children, and findings have been similar.
In terms of vaccine doses administered to date, as of February 7, 2023, a total of 1,185,907
doses were administered. This includes 732,725 first doses. First doses and overall doses
administered peaked in August at the same time when Mpox cases reported to CDC peaked.
Doses administered ha ve declined substantially since August. In the first week of February,
1,314 first doses and 1,243 second doses were administered. While one-third of Mpox cases
occurred among B lack or African American persons, just 13% of first dose vaccine recipients
4 https://www.cdc.gov/mmwr/volumes/71/wr/mm715152a1.htm?s_cid=mm715152a1_w
5 http://dx.doi.org/10.15585/mmwr.mm7144a4
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     were Black or African American. While 31% of Mpox cases were among Hispanic or Latino
persons, just 22% of first dose vaccine recipients were Hispanic or Latino. Additionally, 29% of
Mpox cases were among White persons, while 52% of first dose vaccine recipients were among
White persons. Hence, some substantial differences are observed by race and ethnicity when
comparing those who have been infected versus those receiving vaccine.
JYNNEOS Vaccine Effectiveness
Anna Chard, PhD, MPH (CDC/NCIRD) presented on JYNNEOS VE on behalf of the Vaccine
Task Force of CDC's Mpox Response. The efficacy of JYNNEOS vaccine against Mpox has
been inferred from animal and immunogenicity studies, but it has never been demonstrated in
clinical trials. Additionally, prior to the multinational outbreak, there were no real -world
effectiveness estimates for JYNNEOS against Mpox disease. Therefore, the following key
questions related to VE were developed:
1. What is the effectiveness of JYNNEOS vaccine against Mpox disease for partial (1-dose)
and full (2-dose ) vaccination?
2. Are there differences in VE by route of vaccination administration? On August 9, 2022, an
Emergency Use Authorization (EUA) was issued for intradermal administration of a 2-dose
series to increase vaccine supply, so it is important to examine the differences in VE by
route of administration.
3. Are there differences in VE among persons with immunocompromising conditions? The populations most a t risk for Mpox disease are also at higher risk of immunocompromising
conditions such as HIV .
4. What is the duration of protection conferred from JYNNEOS vaccine? The duration of protection conferred by JYNNEOS vaccine is unknown.
In this presentation, Dr. Chard presented evidence for the first 2 questions ; however, evidence
remains limited regarding VE among persons with immunocompromising conditions and the
duration of protection from JYNNEOS vaccine.
In terms of vaccine performance, Dr. Chard reviewed a study on the incidence of Mpox among
unvaccinated persons versus persons receiving ≥1 JYNNEOS dose in the US.
6 For this
analysis, investigators used surveillance data from confirmed and probable Mpox cases, vaccine administration data ascertained from interviews and immunization registries, and
jurisdiction -specific  estimates of the vaccine- eligible population to compare Mpox instance
among persons who were unvaccinated and those who had received either one or two JYNNEOS doses. There were 9,544 reported Mpox cases among men 18 ─49 years of age from
43 US jurisdictions during the analysis period of July 31─ October 1, 2022. Investigators
estimated weekly Mpox incidence for persons with partial (1 dose) and full (2 doses) vaccination
and persons eligible but unvaccinated. The incidence rate ratio was calculated using negative
binomial regression controlling for week. Mpox incidence among unvaccinated individuals was
7.4 (95% CI = 6.0– 9.1) times as high as persons receiving 1 dose of JYNNEOS vaccine . Mpox
incidence among unvaccinated individuals was 9.6 (95% CI = 6.9– 13.2) times as high as
persons receiving 2 doses of JYNNEOS vaccine. No difference was observed in vaccine
performance between subcutaneous and intradermal administration.
6 Payne AB, et al. Reduced Risk for Mpox After Receipt of 1 or 2 Doses of JYNNEOS Vaccine Compared with Risk Among
Unvaccinated Persons — 43 U. S. Jurisdictions, July 31– October 1, 2022. MMWR Morb Mortal Wkly Rep 2022;71:1560– 1564.
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  The New York City Department of Health and Mental Hygiene (NYC Health) examined the VE of
JYNNEOS administered as PEP using a cohort evaluation of individuals ≥18 years of age
identified through contact investigations to a case patient with Mpox between March 22─ August
24, 2022.7 PEP was defined as receiving the first dose of JYNNEOS within 14 days of exposure
and prior to symptom onset. Case patients were defined as exposed individuals who developed
symptom onset within 21 days of exposure and had laboratory confirmation of Mpox. VE was
77% among individuals who received PEP less than 14 days after their last exposure and 79%
among individuals who received PEP less than 14 days after their first exposure.
Investigators in Israel evaluated the real -world effectiveness of a single subcutaneous dose of
Modified Vaccinia Ankara- Bavarian Nordic (MVA- BN), which uses the trade name JYNNEOS in
the US.8 This was a retrospective, observational cohort study based on data obtained from
electronic health rec ords (EHRs) from a single integrated healthcare organization in Israel. The
cohort included 2,054 men who were eligible for vaccination on July 31, 2022 when the
vaccination campaign began who had completed at least 90 days of follow- up. Specific e ligibility
criteria were males aged 18─ 42 years of age who were dispensed HIV pre-exposure
prophylaxis ( PrEP ) for at least 1 month since January 1, 2022, or males aged 18─ 42 years who
were diagnosed with HIV and also were diagnosed with one or more sexually transmitted
infections (STIs) since January 1, 2022. The time period for this analysis spans July
31─December 25, 2022 such that all participants were followed for 90 to 120 days after cohort
entry. VE was estimated using Cox proportional hazards regression with vaccination status as a
time-varying covariate. The model adjusted for sociodemographic and clinical risk factors.
During July 31─December 25, 2022 there were 5 cases among vaccinated individuals and 16
cases among unvaccinated individuals. The adjusted single- dose VE was 86% (95% CI:
59%-95%) .
In the EPIC -COSMOS case -control study,9 data were used from EPIC ’s EHR platform , Cosmos,
which includes records from over 169 million patients across the US. This was a case -control
design in which cases were defined as patients with an Mpox diagnosis or a positive
orthopoxvirus or positive Mpox virus laboratory result from the study period of August
15─October 29, 2022. Controls were defined as patients with an instant HIV diagnosis or HIV
PrEP prescription during the same study period and was determined based on the
Administration for Strategic Preparedness and Response ( ASPR) vaccine distribution guidance.
VE was estimated using conditional logistic regression models, adjusting for a priori specified confounders. The analysis also was stratified to examine full and partial VE by route of
administration and immunocompromised status. Adjusted VE was 66% for full vaccination and
36% for partial vaccination. Among individuals with no immunocompromising conditions, VE
was 76% for those fully vaccinated and 41% for those partially vaccinated. Although the
analysis was controlled for immunocompromising conditions, VE could not be estimate d among
this population because vaccine coverage was low. Less than 1% of immunocompromised
individuals were fully vaccinated. When examining VE by route of administration, very few
patients were fully vaccinated with 2 subcutaneous doses or 2 intradermal doses. The 95%
confidence intervals were wide, but the point estim ates were similar to the overall estimate. For
fully vaccinated persons with heterologous administration routes, VE was 75% , demonstrating
that 2 doses confers protection regardless of the route of vaccine administration.
7 Unpublished data
8 Sagy, Y. W. et al. Real -world effectiveness of a single dose of mpox vaccine in males. Nature Medicine
https://doi.org/10.1038/s41591- 023-02229-3 (2023)
9 Unpubl ished data
12

  A multi- jurisdictional  case- control study is currently underway. This study examines VE among
men 18─49 years of age who have sex with men and live in 12 US jurisdictions. Cases are
identified through the jurisdictions ’ probable and confirmed Mpox case lists. Controls are
selected from healthcare settings providing HIV PrEP or from STI clinics. Cases are matched to
controls based on time point within 4 weeks of clinic attendance and jurisdiction. Jurisdiction
staff members collect data on participants ’ demographics, exposure history , and vaccination
history using electronic surveys . Vaccination status of enrolled participants is confirmed using
state immunization registries. VE is estimated using multivariable logistic regression with
random intercept for jurisdiction and adjusted for prior specified confounders. Notably, these are
interim results as data collection is still underway. Results indicate that VE is 76% for full
vaccination among those without immunocompromising conditions . VE is 90% for ful l
vaccination. At this interim stage, there were few individuals with partial vaccination or with
immunocompromising conditions. Therefore, data are not sufficiently powered to generate
estimates for these strata.
In a case- control study in New York State (NYS), i nvestigators linked case surveillance data to
the immunization registry. Cases were adult male Mpox cases diagnosed during July
24─October 31, 2022. Controls were adult male STI cases with rectal gonorrhea or primary
syphilis cases during the same time period. Cases and controls were matched on week of
diagnosis and VE was estimated using conditional logistic regression. VE was 68% for partial
vaccination and 89% for full vaccination.
In summary, the existing body of evidence for VE of JYNNEOS against Mpox disease ranges
from 66 % to 83% for full vaccination and 36 % to 86% for partial vaccination. This evidence
indicates that the JYNNEOS vaccine is effective at reducing the risk of Mpox disease. Protection is provided by both 1 and 2 doses of JYNNEO S vaccine , but the highest protection is
provided by 2 vaccine doses regardless of administration route. Further research is needed to
assess whether immunocompromised status modulates VE. Due to small numbers in this
population across studies, there was insufficient power to generate VE estimates among
immunocompromised individuals. Additionally, because of a decline in Mpox cases and the
limited follow- up period from studies to date, further research is needed to assess the duration
of protection conferred by JYNNEOS vaccination.
JYNNEOS Vaccine Safety
Jonathan Duffy, MD, MPH (CDC/NCEZID) noted that while an MMWR report about JYNNEOS
vaccine safety monitoring was published that included data collected through October 2022 , this
presentation would include data through January 2023 collected using 3 surveillance systems :
1) the Vaccine Adverse Event Reporting System (VAERS) , which is a national passive r eporting
system ; 2) the Vaccine Safety Datalink (VSD), which perfor ms medical visit- based active
surveillance for pre- specified adverse events of special interest (AESI) in a population of more
than 10 million people; and 3) v -safe
sm, which is a smartphone -based system that uses text
messaging to initiate web- based survey monitoring for AEs. AEs also were collected as part of
single -patient Emergency Investigational New Drug (EIND) procedures for persons <18 years of
age who were vaccinated before the JYNNEOS EUA was issued that allowed administration in
that age group.
13

 To provide an overview of the VAERS findings, as a reminder VAERS is the national passive
surveillance system for AE reporting after vaccination. VAERS accepts reports from healthcare
providers (HCP) , vaccine manufacturers, and the public. VAERS collects data on any AE
following vaccination, be it coincidental or truly caused by a vaccine. The report of an AE to
VAERS is not documentation that a vaccine caused the event. The FDA issued an EUA for
JYNNEOS on August 9, 2022 that required mandatory reporting to VAERS of vaccine
administration errors , regardless of whether they were associated with an AE; serious AEs
(SAE), irrespective of attribution to vaccination; c ases of cardiac events, including myocardi tis
and pericarditis; and cases of thromboembolic events and neurovascular events.
The analysis presented during this session include d VAERS reports received and processed by
January 20, 2023. AE reporting rates were calculated by dividing the number of V AERS reports
by the number of vaccine doses administered in the US. During the period May 22–January 13 ,
2023, a total of 698,188 people received Dose 1 and a total of 426,980 received Dose 2 for a
total of over more than 1.1 million doses administered. VAERS received 1,817 reports after
JYNNEOS. Most of these reports were for male adults 18─ 64 years of age and for JYNNEOS
given alone without other vaccines on the same day. Most reports were about Dose 1. The most
common route of administration was intradermal, followed by subcutaneous. Intramuscular
administrations also were reported, most of which were reported as an error in the rout e of
administration. Vaccine administration errors were the subject of 50% of all JYNNEOS VAERS
reports. Of these, 96% did not report an adverse health event. Vaccine administration errors
have been reported for JYNNEOS about 3 times more often with intradermal compared to
subcutaneous administration. The most common issue reported with intradermal administration
has been absence of a wheal without vaccine leakage (42%) . CDC's I nterim Clinical
Considerations for use of JYNNEOS state that absence of a whea l without vaccine leakage may
be counted as valid administration . After excluding reports of vaccine administration errors
alone, adverse health events were reported to VAERS at a similar rate for subcutaneous and
intradermal administration. The most common types of events differed slightly by route of
administration. Overall, the most common adverse health events reported to VAERS for adults
were consistent with those reported in pre -licensure clinical trials.
An SAE event is defined as a report of the occurrence of any of the following: d eath, a life -
threatening AE, hospitalization, a persistent or significant incapacity or substantial disruption of
the ability to conduct normal life functions, a congenital anomaly or birth defect, or another
important medical event that based on appropriate medical judgement may jeopardize the
individual and may require medical or surgical intervention to prevent one of the outcomes listed above. About 1% of reports to VAERS after JYNNEOS were classified as SAEs . SAEs were
reported at a rate of 22 reports per million doses administered. SAEs reported to VAERS after
JYNNEOS are listed here:
Myocarditis (n=5)
Death (n=2)**
Pericarditis (n=2) Urticaria (n=2) Appendicitis
Aseptic meningitis
Asthenia Atrial fibrillation Cellulitis
Chest pain Dehydration
Idiopathic thrombocytopenic purpura Injection site discoloration Injection site pain
Injection site scar
Methemoglobinemia Retrograde amnesia Rhabdomyolysis
Sudden hearing loss
14

 Not all AEs that occur after vaccination are caused by the vaccine. Two deaths were reported to
VAERS after JYNNEOS administration. The local Medical Examiners (MEs) determined and
reported the causes of death in these cases to be drowning and cocaine toxicity. Hospi talization
for myocarditis or pericarditis were the most commonly reported SAEs. T he single cases of the
other conditions reported do not suggest safety signals for any of these conditions.
To discuss the myocarditis and pericarditis findings in more detail, m yocarditis and pericarditis
have occurred following either primary vaccination or revaccination with live vaccinia virus
smallpox vaccines in the past. The mechanism is poorly understood, and it was unknown
whether persons who received JYNNEOS might experience myocarditis or pericarditis. In this
epidemiologic analysis, the cases have been classified into 2 groups. The first is myocarditis
with or without pericarditis and the second is acute pericarditis alone. The surveillance risk interval is defined as symptom onset within 30 days after vaccination. In VAERS, 2 cases of
myocarditis were reported after Dose 1 for a rate of 2.75 cases per million persons vaccinated ,
while 3 cases were reported after Dose 2 for rate of 6.74 per million. In the VSD popul ation,
there were 37,646 people who received at least one dose of JYNNEOS. There was 1 case of
myocarditis observed after each dose. The VSD incidence rate estimates have wide confidence
intervals that range from about 1 to 250 cases per million. These confidence intervals overlap
published historical population background rates, which range from 2.7 to 21.6 cases per million persons during a 30- day period. For context, the published historical rates after live replicating
smallpox vaccines have ranged from 70 cases per million after Dryvax in a 2002 military cohort
study, up to 5,000 per million cases after ACAM2000 in a 2018 military cohort study. In
summary, the VAERS and VSD data do not suggest an increased risk for myocarditis following
JYNNEOS compared to expected published background rates,
10 but the possibility of a small
risk cannot be excluded.
In a similar analysis for pericarditis , there were a total of 6 cases reported to VAERS, only 2 of
which were classified as serious due to hospitalization. There were 4 cases after Dose 1 and 2
cases after Dose 2 for a rate up to 5.5 cases per million persons during a 30-day period. There
were no cases identified in the VSD population. The VAERS reporting rate for pericarditis is
similar to expected published historical background rates and less than that observed after live
replicating smallpox vaccines in one military cohort study.11
The v -safesm platform is a smartphone -based system that uses text messaging to initiate web-
based survey monitoring for AEs following vaccination. The data from v -safesm are used to
characterize the basic safety profile of a vaccine when given outside of a clinical trial setting and
can facilitate reporting to VAERS for medically attended adverse events (MAAEs). This system
is meant to supplement CDC’ s other vaccine safety monitoring systems, VAERS and VSD. In
terms of the characteristics of v -safesm participants, there were 181 active participants, defined
as having completed at least one survey between November 16, 2022 – January 29, 2023 , all of
whom were adults and the majority of whom were male. Additional characteristics are shown on
the following tables:
10 References: Halsell, et all. DOI: 10.1001/jama.289.24.3283; Oster, et al. DOI:10.1001/jama.2021.24110; Mandra, et al. DOI:
10.1017/dmp.2020.478
11 References: Imazio, et al. DOI: 10.1136/hrt.2006.104067; Kumar, et al. DOI: 10.1159/000445206; Engler, et al.
DOI:10.1371/journal.pone.011828
15

In terms of the percentage of participants who reported reactions or health impact events at
least once during D ays 0 to 7 after vaccination by dose, a bout 80% reported any injection site
reaction and 5% sought medical care. No participants reported SAEs . The most common type
of injection site and systemic reac tion reported overall was redness at the injection site, reported
by 64% of participants . The most common systemic reaction was fatigue, reported by 40%.
Regarding information about AEs in persons <18 years of age , CDC facilitated single -patient
EIND authorization from the FDA to make JYNNEOS available for persons <than 18 years of
when needed prior to the JYNNEOS EUA being issued on August 9, 2022 that allowed wider
use in this age group. CDC solicited information from vaccine providers about AEs occurring in
their patients during the 28 days after each dose. Persons vaccinated under the EIND ranged in
age from 4 months to 17 years and 58% were male. AEs were reported for 10 (18%) of 57
people after Dose 1 and 5 (21%) of 24 people after Dose 2. The types of events reported
included injection site reactions of pain, erythema, swelling, and induration and systemic AEs of
fever, fatigue, and headache. No SAEs were collected in this project.
VAERS also was used to collect data on persons <18 years of age . JYNNEOS was
administered to 1,245 persons <18 years of age in the US during the surveillance period.
VAERS received 25 reports for this age group. Vaccinated persons ’ ages ranged from 12
through 17 years. Reports of vaccine administration errors accounted for 84% of these reports,
with the most common being intradermal administration instead of subcutaneous, which is the
authorized route for this age group. The only AE reported was 1 person with syncope and no
SAEs were reported.
The overall conclusions about vaccine safety monitoring are that JYNNEOS post -licensure and
post-authorization vaccine safety surveillance findings to date are consistent with those
observed in clinical trials. No new or unexpected safety concerns have been identified. SAEs
were rare among adults and none have been identified among persons <18 years of age .
VAERS and VSD data taken together do not suggest an increased risk for myocarditis or
pericarditis following JYNNEOS, but the possibility of a small risk of myocarditis cannot be
excluded.
16

   Mpox Vaccine Acceptability and U ptake from Cross-S ectional S urveys
Kevin P. Delaney, PhD, MPH (CDC/NCHHSTP) presented Mpox vaccine acceptability and
uptake findings from cross -sectional surveys from among clinicians and vaccine interest, intent,
and uptake among the general population and populations disproportionately affected by the
current outbreak on behalf of the CDC Community Engagement Task Forc e. One source of
information for this is surv eys of clinicians . CDC has worked with Sermo to get some insights on
this. Sermo is an online community of more than 1.3 million clinicians. At the beginning of
August, the company conducted what they call a “B arometer ” survey of physicians around the
world with over 1,000 physicians total.12 During this session, Dr. Delaney p resented data from
the 415 US -based clinicians in that survey. He highlighted that in early August 2022 , the
majority of clinicians surveyed wanted more access to Mpox vaccine. At short follow -up was
conducted on September 12, 2022 at CDC’s request that found both high vaccine demand and
acceptability, with 76% of respondents saying they knew where to send patients for JY NNEOS
vaccine. More importantly, 86% wanted to be able to offer vaccine in their practice.
In terms of information from affected populations, this table provides an outline and overview of
the 4 surveys conducted by CDC and partners during the current out break :
The first survey is one that CDC conducted in partnership with Porter Novelli. Porter Novelli is a
contractor who conducted 4 online general population surveys of US adults through the months
of August, September, October, and December 2022 on knowledge, attitudes, and beliefs of
Mpox -related topics. The data are weighted to match US Census proportions for age, gender,
region, race, ethnicity, and education. They also ask a question about whether the respondent
considered themselves to be a membe r of the lesbian, gay, bisexual, transgender, queer or
questioning,  or other ( LGBTQ+ ) community. The December survey had the largest sample and
asked several questions specifically designed to directly measure Mpox vaccine acceptability and value. In this general population survey, very few people overall disagreed with the
statement that “The monkeypox vaccine is safe. ” Although many of the general population, even
those identifying as part of the LGBTQ+ community , said they did not know. For the current
outbreak, which overwhelmingly has affected gay and bisexual men, 51% of those who
identified as LGBTQ+ thought the vaccine was safe and 50% of that group also thought it was
important to get the Mpox vaccine to protect themselves. For the second q uestion, it is
12 https://app.sermo.com/barometer/unitedstates
17

   interesting that 31% of those who did not identify as LGBTQ+ or a member of the LGBTQ+
community also felt it would be important to get the Mpox vaccine to protect themselves.
The American Transformative HIV Study (AMETHST )13 collected data from the community most
affected by the current outbreak (e.g., gay, bisexual, and other MSM) . AMETHYST is a National
Institutes of Health ( NIH)- funded online cohort that will eventually include 5,000 sexual minority
men. This is a diverse group with higher risk of HIV acquisition than the general population,
even of sexual minority men, by design. The study will be recruiting such that the cohort is no
more than 50% non- Hispanic Whites, the majority -minority, by race and ethnicity. About 60% of
the cohort will have reported recent methamphetamine use, which increases bio- behavioral
vulnerability to HIV. To achieve the objective of enrolling 5,000 such men, the plan is to screen
over 30,000 respondents with an online eligibility survey. Questions about Mpox knowledge,
vaccine uptake, and behavior change have been added to the screening enrollment survey. The
data presented during this session were from the first 8,500 participants screened from August
6─November 15, 2022.
Regarding the question, “How mu ch have you worried about Mpox infection over the last 2
weeks?” the number who said they worried some or more than half of the days decreased from
66% in August to 35% in November and the number who said they never worry increased from 34% in August to 66.4% in November. While Mpox concern decreased over time, about one-
third of participants remain concerned about Mpox. Over 85% of respondents remain interested
in vaccine. Vaccine coverage doubled between August and September but then flattened out,
which is consistent with vaccine administration data. As of November, 30% of those recruited
reported having received at least 1 dose. However, the proportion of people reporting the intent
to take vaccine remained strong and there was minimal increase in the proportion of people who
said they were unlikely to get vaccinated. Overall, 85% of those enrolled in the survey so far are
either vaccinated or reported being likely to get vaccinated. In terms of vaccine uptake by race
from August to November 2022 among AMETHYST participants surveyed at the peak of the
outbreak, Black men had the highest proportion reporting receipt of at least 1 dose of vaccine.
In August, Black participants had higher vaccine coverage than participants from other racial and ethnic groups but did not see the “doubling” in vaccine coverage that were reported overall.
It also is important to think about other communities in terms of equity. AMETHYST may be the
only or best source for this. There was much lower uptake of vaccine for gender div erse
persons and for those who do not identify as gay. Moving forward with plans to improve equity
and access, it is important to do a better job of specifically marketing and creating demand for
those groups as well as Black men.
The American Men’s Internet Survey (AMIS) is an Emory University annual online cross -
sectional survey of people who were born and currently identify as male that is typically
conducted with recruitment from October to February of a given year. In August 2022,
colleagues at Emory University conducted a special one- time survey that recontacted men who
participated in the 2021 AMIS survey cycle interviewed between October 2021 and February
2022 to explore knowledge, attitudes, and practices related to the US Mpox outbreak. The
survey was conducted between August 5 -15, 2022 during the peak of the current outbreak.
14
For those interested, Emory posted all of the questions that were asked in the August survey
online. There are questions in this survey about vaccine knowledge, access , and desire to be
vaccinated; barriers to vaccination; and sources of information on Mpox. As published in an
MMWR that first appeared online on August 26th, 53% of AMIS participants reported concern
13 https://grants.nih.gov/grants/guide/rfa- files/RFA -AI-21-018.html
14 https://www.cdc.gov/mmwr/volumes/71/wr/mm7135e1.htm
18

  about getting Mpox at that time. At that time, 18.6% of MSM surveyed reported having received
at least 1 dose of vaccine. This is consistent with the AMETHYST data. That MMWR also
reported higher vaccine uptake for Black men compared to all other racial groups, lower vaccine
uptake in more rural areas relative to urban areas, and lower vaccine uptake in the South and
Midwest. At the time this was published, the MMWR called for more equitable vaccine delivery.
These quotes are from the discussion section:
“Equitable vaccine program implementation involve…, engaging diverse partners
already working with special populations, delivering vaccines through mobile outreach
and pop- up events, and diversifying times and locations for vaccine administration”
“Expanding vaccine availability geographically, including diversifying vaccination locations to include nonurban areas, can help ensure that those who need vaccination
have access to it.”
Just 4 days after publication of the MMWR , the White House announced plans to support
expansion of vaccine access th rough distribution to groups working to provide vaccine at large
events and in spaces where they could reach populations who otherwise might not have
access.
15 The Mpox Vaccine Equity Pilot Program (VEPP) was created to: 1) support innovative
ways to address vaccination disparities; 2) encourage vaccination coordination between health departments and community -based organizations (CBOs); and 3) promote innovation to
strengthen existing vaccination infrastructure. The VEPP provided additional vaccine above the
original allocation to 15 jurisdictions, 14 states, and Puerto Rico for 28 different vaccination programs and events. These were beyond the threshold supplies provided to states. This
project delivered nearly 25,000 doses of vaccine at special vaccine equity events.
The 2022- 2023 AMIS is still recruiting. These data are from an abstract developed for
submission to the International AIDS Society (IAS) meeting but are not yet published.
Recruitment began in early October and by the end of December, over 3,000 men had been
enrolled. At that point, 33% reported that they had received 1 dose of vaccine. Again, very
consistent with the AMETHYST data for November and December. Vaccine uptake was
associated with Mpox awareness and concern and also with factors that might be indicative of
concern for or awareness of sexual health and access to sexual health services overall,
including HIV care, STI testing, and HIV PrEP use.
A study conducted by the CDC and the San Francisco Department of Public Health (SFDPH)
specifically recruit ed another special population of people experiencing homelessness in San
Francisco. This study was fielded from October 23─November 5 and sought to understand
Mpox vaccine coverage and acceptability among peopl e experiencing homelessness. This
study also collected blood to assess seroprevalence in this community, though Dr. Delaney did
not discuss that during this session. The take- home from this analysis is that 56% of those who
reported any sexual risk and 74% of MSM, said that they would accept Mpox vaccination.
Again, consistent with the AMETHYST data.
15 https://www.whitehouse.gov/briefing- room/statements -releases/2022/08/30/fact -sheet -white -house- monkeypox -response- team -
announces -new-plans -to-support -large- lgbtqi -events -and-equity -interventions -to-reach- communities -at-highest -risk-of-
contracting- the-virus/
19

  Interim Clinical Considerations
Rosalind Carter, PhD (CDC/NCIRD) provided a brief overview of CDC’s Mpox vaccine Interim
Clinical Considerations (ICC) that were developed to guide vaccine implementation during the
Mpox outbreak. It is important to remember that the ICC is a living document . As the
epidemiology of the outbreak evolved and as feedback was received from the field in terms of
new questions and concerns, the guidance was updated or clarified. The latest ICC updates
continue to emphasize the importance of vaccination before exposure for those with the highest
potential for exposure to Mpox, the importance of identifying and vaccinating persons living with
HIV or who have other causes of immunosuppression who have had recent or anticipate
potential Mpox exposure, and including explicit language stating that the definitions of risk
groups also include adolescents.
From the beginning of the 2022 Mpox outbreak, the US Government (USG) recognized that
Mpox vaccine availability was the critical strategy to limit the rapid spread of Mpox. Two
vaccines may be used for prevention of Mpox and were available from the Strategic National
Stockpile (SNS) . They included the JYNNEOS vaccine approved for prevention of smallpox and
Mpox and licensed for use among persons 18 years of age and older. On August 9, 2022, FDA
issued an E xpanded Use Authorization (EUA) for intradermal administration among persons 18
years of age and older. That is the primary vaccine being used during this outbreak in the US.
ACAM2000 is an alternative to JYNNEOS and approved to protect against both smallpox and
monkeypox. While it is available, it has not been used duri ng this outbreak due to the higher risk
of SAEs .
On June 28, 2022, the federal government announced an enhanced nationwide strategy to
vaccinate and protect people at risk for Mpox, prioritize vaccines for areas with the highest
number of cases, and provide guidance to state, tribal, local, and territorial health officials to aid
planning and response efforts. Multiple federal agencies, including the ASPR, SNS, Biomedical
Advanced Research and Development Authority (BARDA) , CDC, and FDA are working closely
with partners to ensure there are enough vaccine doses available to vaccinate all people for whom vaccine is recommended. There are 2 primary strategies, which are 1) vaccination of
individuals after known or presumed exposure to someone with Mpox ; and 2) vaccination prior
to exposure among persons at high risk for potential exposure.
For PEP in the first strategy , CDC has defined people eligible for vaccine in the ICC as follows:
People who are known contacts to a person with Mpox, and identified by public health
authorities as a “contact” from case investigation, contact tracing, or risk exposure
assessment ; or
People who are aware that a recent (within the past 14 days) sex partner was diagnosed
with Mpox ; or
Gay, bisexual, other MSM , and transgender or non- binary people (including adolescents )
who have had sex with multiple partners , at a commercial sex venue, or sex in an
association with an event, venue, or defined geographic area where Mpox transmission is
occurring.
20

  For PrEP in the second strategy, CDC has defined eligible groups in the ICC as those groups
eligible for vaccination prior to Mpox exposure who either have highest potential risk for
exposure or who anticipate potential exposure to Mpox :
Gay, bisexual, and other men who have sex with men, and transgender or nonbinary people (including adolescents) who, within the past 6 months, have had:
− A new diagnosis of one or more sexually transmitted diseases (e.g., chlamydia, gonorrhea, syphilis);
− More than one sex partner
People who have had any of the following in the past 6 months:
− Sex at a commercial sex venue; or
− Sex in association with a large public event in a geographic area where mpox transmission is occurring
Sexual partners of people with the above risks
People with HIV † infection or other causes of immunosuppression who have had recent or
anticipate potential mpox exposure
People in certain occupational exposure risk groups (laboratory personnel working with orthopoxviruses )
This is all in accordance with the ACIP 2022 recommendations. It is important to note that although the language describes the highest risk groups in an effort to improve equitable access
to Mpox vaccines, persons who request vaccination can receive it without having to attest to
meeting any of these specific criteria.
Health equity principles outlined in the interim clinical guidance are incorporated into the National Vaccine Strategy as well as local implementation efforts. Some of these principles
include engaging people from affected communities in the planning and design of vaccination
efforts ; using non- stigmatizing, plain language; reiterating privacy of information and how data
will be used; engaging diverse partners already working with special populations ; bringing
vaccines to where affected populations are (e.g., pop- up events, mobile outreach); offering
multiple appointment times and flexible walk -in opportunities, including evenings and weekends
to improve vaccine accessibility ; leveraging clinical venues such as the Federally Qualified
Health Centers (FQHCs) that serve people who have historically had less access to primary
care, sexual health clinics, transgender health clinics, and pharmacies to deliver vaccines; and
minimizing systems that are first come, first -served.
Looking quickly at the data, almost 1.2 million doses were administered and reported to CDC
through February 7, 2023. This includes 734,000 first doses and 452 second doses. During the
week of August 7- 13, the EUA for intradermal administration was introduced. At tha t same time,
additional vaccine vials were released from the SNS and provided to the states. Intradermal
dosing greatly expanded the number of people vaccinated with first and second doses during
the peak of the outbreak when demand was highest. Looking at data comparing Mpox cases to
those vaccinated by race and ethnicity and whether vaccine equity improved over time, notably
completeness for race and ethnicity data in vaccine administration database was very good quality. Over 91% of this information was completed. Summariz ing the overall data from May
through the end of January 2023 compared to the time periods of mid-June to mid -July and mid-
July to mid -August, the proportion vaccinated who were Hispanic increased from 19% to 23%
and the proportion of people vaccinated who were Black non- Hispanic increased from 7% to
13%. While t hese proportions were maintained over time, improvements in vaccine equity in
subsequent months have been modest . It is important to note that the se data summarize the
21

   national picture and individual jurisdictions, including many of the highest burden states that
have made substantial progress in addressing equity gaps. Nonetheless, there is much work
ahead in implementation to improve vaccine equity.
To highlight a few elements of the current vaccine implementation as best practices for future
outbreaks , vaccine strategies and implementation were adapted to local situations, local
epidemiology, and population needs. This included adapting the eligi bility criteria for local
contexts. Some examples of this are that some states included sex workers in their definition of
vaccine eligibility. Many others removed sexual orientation labels from eligibility criteria and
reduced potential stigma by allowing people to self -attest to eligibility. The interim guidance for
eligibility also evolved as the epidemiology , which was very dynamic, changed over time. CDC
recognizes that vaccination offered in the context of broader prevention activities, as well as
sexual health care, including HIV testing and PrEP initiation, increased access to vaccines as
well as acceptance of vaccines. The importance of the key role that CBOs had cannot be
emphasized enough in the success of vaccine implementation , both as trusted messengers and
in logisticians in helping set up vaccine events in their neighborhoods and communities. It also
is important to highlight the importance of planning resources for data collection, including
collecting vaccine status and dates of vaccination on monkeypox reporting forms, which allowed
CDC to measure vaccine performance early in the rollout. Includ ing race and ethnicity data on
vaccination reports, including on reports shared with CD C, is essential in driving program
actions and course correction.
In addition to the success stories, there were many challenges, most notably the limited supply
of vaccine at the peak of the outbreak in mid- July when demand was high. The intradermal
route of administration was an important public health intervention, increasing the vaccine
supply 300% to 500% when it was most needed. CDC’s ASPR colleagues handled the complex
logistics of moving JYNNEOS vaccine from the federal SNS to the jurisdictions. However, at the
beginning, the SNS was limited to only 5 shipments per week during the outbreak peak, leaving
the jurisdictions to manage redistribution to providers in critical areas. However, within about 6
weeks, ASPR was able to increase their shipping capacity to provide directly to providers. The
change from subcutaneous to intradermal administration required jurisdictions to provide skills
training to vaccinators. However, on average, these jurisdictions were able to begin implementation of intradermal within 2 to 3 weeks of the EUA, which was a significant
accomplishment and heavy lift. Initially, health departments and public clinics were the primary
vaccine providers, providing more than 50% of all vaccinations. As the outbreak has subsided,
the jurisdictions have increasingly engaged STI and HIV care providers, as well as pharmacies
in some states to take on these roles. Despite these challenges, it is important to acknowledge
the dedication and the hard work of the jurisdictional health departments that are truly
responsible for the successful implementation of Mpox vaccines.
EtR: Use of JYNNEOS During Mpox Outbreaks
Agam Rao, MD (CDC/NCEZID) presented the EtR Framework for vaccination with JYNNEOS
vaccine during any monkeypox outbreak that could be spread through travelers from countries
where it is endemic, imported animals such as prairie dogs or other animals, et cetera . It is
important to understand that even though a vote is being proposed for JYNNEOS for any
outbreak, the current outbreak is not over and people are encouraged to continue to be
vaccinated based on the ICC that Dr. Carter summarized for specific populations for whom
JYNNEOS is recommended during the current outbreak. Dr. Rao cautioned that this
presentation included photographs that might be difficult for some viewers and that she would
provide advanced notice before showing them.
22

  As a reminder, the EtR F ramework is a structure to describe information considered in moving
from evidence to ACIP vaccine recommendations. It provides transparency around the impact of
additional factors on deliberations when considering a recommendation. There are 7 Et R
domains : Public Health Problem, Benefits and Harms, Values, Acceptability, Equity, Feasibility,
and Resource Use. Dr Rao presented the WG’s interpretation of the data for each of these
domains and the response to the associated questions for each domain. The EtR question is :
Does ACIP recommend the2- dose* JYNNEOS vaccine series for persons aged 18 years
and older at risk of Mpox during an Mpox outbreak? §
*Dose 2 administered 1 month after Dose 1
§Public health authorities will determine whether there is an Mpox outbreak ; a single case may be considered an Mpox
outbreak at the discretion of public health authorities. Other circumstances in which a public health response may be
indicated include ongoing risk of introduction of Mpox into a community due to disease activity in another geographic area.
In terms of the P ublic Health Problem domain, there have been several notable public health
events involving Mpox since it was first recognized in humans in 1970. Early cases were in rural
settings in certain forested regions of Africa where the presumed animal reservoirs reside. The
first outbreak outside of Africa occur red in the US in 2003 from pet prairie dogs that were co-
housed with infected small mammals from Ghana. There were 47 cases associated with that
outbreak. Going forward, cases continue to occur in Africa. The 9 African countries are the
countries where we know that cases had occurred. Cameroon, Central African Republic, Côte
d'Ivoire, Democratic Republic of Congo, Gabon, Liberia, Nigeria, Republic of Congo, and Sierra Leone. In 2017, there was a large outbreak in Nigeria involving 17 states . At that time, it was
considered a very large outbreak involving 138 cases. During 2018─2021, there were imported
cases in travelers from Nigeria to various countries, to the UK and Israel in 2018, and to the UK
and Singapore in 2019. In 2021, there were 3 cases, 2 of which occurred in the US. In 2022, a
multinational outbreak occurred. All of this to say that Mpox does seem to be of public health significance and importance. There have been a lot of cases, including a reemergence of
human cases in recent years after decades of no reported cases in some countries.
Even before the 2022 multinational Mpox outbreak , investigations for even a single case of
Mpox have been intense. During the July 2021 investigation, in one of the investigations in the
US 223 contacts had to be monitored. Fortunately, there were no high- risk exposures or
secondary transmissions. There were a lot of contacts, including flight crew and fellow passengers on inte rnational and domestic flights and friends of the affected patient and a
rideshare driver . All of these individuals were monitored by public health authorities. There were
2 imported cases to the UK in 2019 and 2021 that resulted in secondary infections. In 2019, a
HCW developed Mpox after presumed exposure while changing the bedding of an Mpox
patient . In 2020, 2 household contacts of an Mpox patient developed Mpox. This outbreak is
obviously involved in many cases that peaked in early August . Case counts are decreasing at
this time, but this outbreak is not over.
The typical presentation manifestation of Mpox during the current outbreak are small, firm,
deep- seated,  well-circumscribed lesions that can occur on the palms , soles, and other parts of
the body. They often have been scattered or focused on one body part, most commonly the
genitals. Prodromal symptoms, including fever and lymphadenopathy, have inconsistently occurred. When lesions have occurred in the peri anal or genital region, the pain from lesions
has been particularly pronounced. Rectal pain, abdominal pain, rectal bleeding, and tenesmus
have all been reported. Typically, symptoms resolve with supportive care alone, including pain
control. However, severe manifestations are occurring in some patients who have severe
outcomes. Severe manifestations include ocular lesions, neurologic complications,
23

  myopericarditis, and certain mucosal lesions that can affect patients regardless of immune
status. Myopericarditis cases have been seen in people who developed Mpox . not just in
individuals. Keratitis and conjunctival ulcer are associated with ocular Mpox. Ocular lesions can
be very serious and can even cause blindness, as in other countries where classic Mpox has
occu rred in Africa. Myopericarditis and neurologic complications have been reported in a small
number of patients who are uncertain of the reasons for this. It has occurred in individuals who
have been immunocompetent. Encephalitis and transverse myelitis have occurred in patient s
with Mpox. When lesions occur on certain mucosal surfaces (e.g., urinary meatus, penis ) they
can cause complications, including obstruction.
Lesions can be severe, necrotic , and require consultation from medical subspecialists such as
urologists, gastroenterologists, and general surgeons depending upon the location of the
lesions. While these are considered severe manifestations, the most severe and the life-
threatening lesions occur in patients with severe immunocompromise. Patients who are
severely immunocompromised due to advanced HIV in particular have had the most severe
manifestations of Mpox during the current outbreak. The etiology is believed to be uncontrolled
viral spread in severe ly immunocompromise d patients . Dr. Rao shared some images to illustrate
the progression of illness and how different the lesions in these patients can be from the typical
presentation. Medical therapeutics such as t ecovirimat and brincidofovir may be helpful, but an
optimized immune system through antiretroviral therapy , temporary halting of immunomodulator
therapies , or some other mechanism is still the most critical aspect of care. Deaths have
occurred because of these illnesses, often many weeks after hospitalization because of the
progression and despite therapeutics. Therefore, the WG determined Mpox outbreaks to be of
public health importance based on all of the data presented .
Regarding the Benefits and Harms domain, there are early estimates and population- based
estimates of VE. Vaccine performance has been evaluated through comparison of incidence of
Mpox between vaccinated and unvaccinated persons in 43 US jurisdictions. Mpox incidence
among unvaccinated was 7.4 times that among persons who received only 1 dose of JYNNEOS
vaccine ≥14 days earlier , and 9.6 times that among persons who received Dose 2 ≥14 days
earlier . Population -based adjusted measures of VE using EMRs also have been performed . A
retrospective population- based cohort study conducted in Israel showed that 5 Mpox infections
occurred among subjects vaccinated with 1 subcutaneous dose and 16 infections occurred
among unvaccinated subjects. The VE for Dose 1 was calculated as 86% with the confidence
interval of 59 % to 95%. A nationwide US case -control study with a 1:4 ratio of cases matched to
controls had an adjusted VE of 35.8% with a 95% confidence interval of 22.1% to 47.1% for 1
dose and 66% with a 95% confidence interval of 47.7% to 78.1% for 2 doses, regardless of the
vaccination route. In terms of p opulation- based adjusted measures of VE using case -control
studies , a case- control study of adult MSM 18─49 years of age in 12 US jurisdictions had an
adjusted VE of 76% with a confidence interval of 48% to 89% for the 2 doses. Those are interim
results. This study is ongoing, so the WG hopes to have more information to present during the
June 2023 ACIP meeting. Unpublished preliminary results from a NYS case -control study of
adult male Mpox cases matched to STI controls had an adjusted VE of 68% with a confidence
interval of 25 % to 86% for 1 dose and 89% with a confidence interval of 44 % to 98% for 2
doses. These also are preliminary results and the analyses are ongoing.
24

 In terms of PEP effectiveness and infections following a single JYNNEOS dose
10% (11 out of 108 subjects ) in France who were administered JYNNEOS after Mpox exposure
became symptomatic with Mpox disease soon after vaccination. The interquartile range was 1
to 6 days, with a median of 5 days . Notably, the clinical course was mild among those persons.
Also in France, there was an observational study involving people who received a single
subcutaneous dose. In this study , 4% were infected during the month after the vaccination and
none had serious infection. In a NYC cohort study of individuals with high- risk exposure , VE was
77% with PEP <14 days after last exposure and 79% with PEP <14 days after the first
exposure. B ased on all of this information that seemed to support the benefits of the vaccine,
the WG’s interpretation was that the desirable anticipated effects of Mpox vaccine during an
outbreak are large.
Vaccine safety is focused on the subcutaneous route of administration during May 22, 2022
through January 13, 2023. A total of 1,125,168 JYNNEOS vaccine doses were administered.
CDC monitored JYNNEOS safety using VAERS and VSD for vaccine recipients of all ages. The
most common AEs reported were non- serious and included injection site reactions consistent
with pre -licens ure studies. These were reported at similar rates for doses received by
intradermal and subcutaneous administration and SAEs were rare among adults. The WG’s
interpretation is that the undesirable anticipated effects of Mpox vaccine during an outbreak are
small. The WG’s interpretation of the balance between the desirable and undesirable effects
was that the desirable effects outweigh the undesirable effects and favored the intervention of
vaccination with JYNNEOS.
Regarding the Values domain, surveys have been used to assess the values of the individuals
who are being vaccinated during the 2022 outbreak. Even though this vote is for Mpox
outbreaks in general that may not be specific to male- to-male sexual contact, there are data
from this outbr eak to rely on to answer this question. In terms of populations at highest risk of
Mpox, and August AMIS survey found that 53.1% of respondents had concerns about getting
Mpox. During October ─December, an AMIS survey showed that those with high Mpox concer n
had a 3.5 times odds of being vaccinated. Interest in the vaccine seemed to be high during
August ─November when greater than 85% of respondents in the AMETHYST study were
interested in the vaccine. During August ─December, 50% of Porter Novelli survey res ponders
who identified as LGBTQ+ felt that the vaccination is important to protect from Mpox. That
includes not only MSM, but also other LGBTQ. During October ─November, greater than 70% of
MSM in a San Francisco survey of persons experiencing homelessness reported that they
would accept or have accepted vaccination. This is important because a disparity has been
observed in that individuals experiencing homelessness have experienced a disproportionate
number of cases just as those who are B lack and Hispanic have. The WG’s interpretation was
that the target population probably feels that the desirable effects are large relative to the
undesirable effects .
There is some uncertainty or variability in how many people might value the vaccination. During
the 2022 Mpox outbreak, willingness to be vaccinated was dynamic and depended upon
perceived vulnerabilities. Clear demand for JYNNEOS vaccination occurred, but many still
remain unvaccinated for unclear reasons. The demographics of future outbreaks also would be
unclear, which is why the WG believes there might be some uncertainty or variability. It is
unknown what the demographics of future outbreaks might be , who the affected populations
might be, and whether the values expressed by the population most affected by the 2022 Mpox
outbreak can be extrapolated to all other populations. For this reason, the WG’s interpretation
was that there is possibly important uncertainty or variability.
25

    Moving to the Acceptability domain, stakeholder perceptions are very important to this question.
Sermo is an online community of greater than 1.3 million clinicians. During July 31─ August 1,
2022, survey results of US clinicians (n=415)  showed that 69% felt that the US was without
enough Mpox vaccine to handle the outbreak, indicating that they wanted vaccine to be
available. A September 12, 2022 survey among 62 US clinicians showed that 66% had treated
at least 1 Mpox patient, 76% knew where a patient could get JYNNEOS vaccination, and 86%
wanted to be able to prov ide vaccination to their office. Taken together, the WG interpreted this
as the clinician stakeholders being supportive of vaccination.
In terms of health departments and CBOs, h ealth departments have been requesting JYNNEOS
and organizing vaccination campaigns. Approximately 70% of the allotted JYNNEOS vaccine
doses already have been requested and shipped to states in response to requests from
stakeholders. In addition, the VEPP has enabled jurisdictions to request more than their allotted
amount of JYNNEOS vaccine. It was established to support innovative ways to address
vaccination disparities, encourage vaccination coordination between health departments and
CBOs, and promote innovation to strengthen existing vaccination infrastructure. A total of 28
programs involving 15 jurisdictions and approximately 25,000 doses have been associated with the VEPP. This is above and beyond the initially allotted amounts, all of which illustrates that
there seems to be support among stakeholders, health departments, and CBOs . The WG’s
interpretation is that the intervention is acceptable to key stakeholders .
Regarding the R esource Use domain, JYNNEOS vaccine is provided from the HHS SNS free of
charge. Vaccines are a good use of resources during an outbr eak and this E tR and ACIP vote
are intended for any outbreaks. However, there are costs and challenges associated with
mobile pop- up vaccination sites . A cost- effectiveness analysis of vaccine implementation during
the current outbreak is not currently ava ilable. As comments during previous sessions have
indicated, use of the SNS is sometimes not as efficient as would be preferred. The WG was split
on their interpretation of whether the intervention is a reasonable and efficient allocation of
resources.  Some WG members felt that it was reasonable, but that the efficient element was
uncertain. Therefore, the interpretation was that it varies.
With respect to the Equity domain, no groups or settings are disadvantaged by a
recommendation for JYNNEOS use during Mpox outbreaks. Effectiveness is the same for all
immunocompetent persons. Implementation to assure equitable access will be important,
particularly among persons who are at high risk for severe outcomes. This recommendation by
ACIP might facilitate broad acceptance of the vaccine (e.g., by insurance companies and health
departments ) because it is an endorsement by ACIP after rigorous review of the evidence. The
WG’s interpretation was that interpreting equity as independent of implementation challenges,
the impact on health equity is that equity probably would be increased.
In terms of the F easibility domain, the feasibility of conducting vaccine campaigns in
communities , at events , and within the public health facilit ies was demonstrated in 2022.
Vaccinations can be integrated into provider ’ practices . Standing orders are available, the IIS
requirements for reporting vaccinations are the same as for COVID -19 vaccines, and JYNNEOS
can be stored refrigerated for 8 weeks. A wide range of vaccinators can administer JYNNEOS
unlike the other orthopoxvirus vaccine, which some clinicians are hesitant to administer . All of
these elements support the feasibility of vaccines and the vaccine recommendation. which some clinicians ar e hesitant to administer. The WG thought carefully about this and felt
that the JYNNEOS vaccination probably is sustainable during outbreaks. Vaccine access is an important concern. There needs to be increased , convenient , and low stigma access for all
persons  who might be at risk . Considerations to ensure vaccine equity include strong ties with
26

 CBOs , support for vaccination events, engagement of trusted messengers, and ensuring that
there is access, including in rural areas. The WG’s interpretation was that the intervention is
feasible to implement.
To summarize the responses to all of the E tR questions, the WG felt that there was possibly
important uncertainty or variability, mostly because they did not have data about stakeholders
who might be affected d uring other types of Mpox outbreaks. The WG felt that it is reasonable to
have vaccines during an outbreak if it would prevent infections, which the Mpox vaccine does.
There was some concern about whether use of this intervention is an efficient allocation of
resources , so the WG’s interpretation of whether the intervention is reasonable and efficient
allocation of resources is that this varies . In terms of the balance of consequences, the WG felt
that the desirable consequences clearly outweigh the undesirable consequences in most
settings and drafted the following proposed recommendation language for ACIP’s consideration:
ACIP recommends the 2-dose* JYNNEOS vaccine series for persons aged 18 years and
older at risk of Mpox during an Mpox outbreak? §
*Dose 2 administered 1 month after Dose 1
§Public health authorities will determine whether there is an Mpox outbreak; a single case may be considered an Mpox
outbreak at the discretion of public health authorities. Other circumstances in which a public health response may be
indicated include ongoing risk of introduction of Mpox into a community due to disease activity in another geographic area.
The WG also proposed the following Clinical Considerations :
In an outbreak setting, vaccine is ideally given pre- exposure but may also be given as post -
exposure prophylaxis (PEP) , although evidence has not been reviewed by ACIP for PEP at
this time.
The complete 2- dose vaccine series should be given regardless of the timing of the
exposure.
Although ACIP has not reviewed the evidence, if there are vaccine supply shortages, the
intradermal route of administration can be used.
The WG will be talking more about data for the intradermal route of administration during the
June ACIP meeting. The entire outbreak language from this meeting and the June meeting will
be consolidated into one MMWR after that. During the June ACIP meeting, the WG will provide
updates about VE and safety and will propose a separate vote for administration of the
JYNNEOS vaccine in people less than the age of 18 years. The focus during this meeting was
on persons ≥18 years partly because that is simply an expansion of the 2022 ACIP
recommendations for persons at occupational risk. It is the same age range, but for a different
group of people. Depending upon the epidemiology of this outbreak, if cases are continuing to
occur in large numbers, there will be more discussion and consideration for a longer -term
vaccination strategy with the 2- dose JYNNEOS series during the October 2023 ACIP meeting .
ACIP Discussion Points, Observations , Suggestions on Mpox Vaccine
Following Dr. Ellington’s Presentation
• It would be beneficial to have additional details on the individual who had a spontaneous
abortion.
Following Dr. Chard’s Presentation
• Concern was expressed about the large difference in the estimates of single dose coverage.
27

  • It would be beneficial to have information about whether delivering vaccine too deeply
affects VE.
• Concern was expressed about very few people being able to administer intradermal vaccine anymore. Dr. Rao emphasized that early on the intradermal route was recommended due to the shortage of vaccine. There is more vaccine available now and route of administration should not be a reason someone is not vaccinated.
• In the future, it would be helpful to share VE estimates of people with different organ transplants taking different pharmaceutical medications and HIV diagnosis codes .
• As more information is collected on intradermal versus subcutaneous administration, it would be useful, if possible, to look at that combined with full versus partial vaccination
to understand if there is any differential impact in the setting of an outbreak if there is a preference for one or the other.
Following Dr. Duffy’s Presentation
• While it is reassuring that the rate of myocarditis/pericarditis is lower than following Dryvax, the numbers of people vaccinated are still very small.
• In response to a request for the benefit of the public to explain what it means to have an absence of wheal without vaccine leakage, Dr. Buffy indicated that with intradermal administration, the idea is that there will be a wheal or small area where the skin is
raised after an injection. Some people have reported to VAERS that when they have
attempted intradermal administration but have not seen a wheal forming. That is why
CDC issued some guidance to indicate that just because the wheal is not seen does not
mean that the intradermal vaccination was not successful.
• This is another example that reveals that the US has a multifaceted safety surveillance system in which each platform complements the other in terms of strengths and limitations.
• Though v -safe
sm had low uptake for Mpox, with the understanding that this likely was a
timing issue, it is laudable that CDC plans to use this system in the future for other types
of vaccines and that in non- emergency response and routine vaccination programs, it is
expected to be available early in the launch of new vaccines.
• It would be beneficial to have information on JYNNEOS vaccine in pregnancy. Dr. Buffy
indicated that v -safesm has a question about pregnancy.
• Monitoring vaccine safety in general in pregnancy and among immunocompromised
persons is crucial. The lessons learned from COVID -19 in terms of these populations
have been very positive and reassuring, which is extremely helpful in terms of communication efforts.
Following Dr. Delaney’s Presentation
• Regarding a question about what types of practices were involved in the Sermo cross -
sectional surveys, Dr. Delaney indicated that most clinicians surveyed were from primary care or infectious disease practices. In terms of geography and racial distribution, they
were primarily in the Northeast. The survey was quick and was open for only about 48
hours. The follow -up survey included a more diverse pool of respondents from the US.
The data are available online.
• Looking at safety data, efficacy data, and outreach is a good approach in general in
terms of how ACIP views a theoretical upcoming vote on this vaccine.
• It would be beneficial to hear more about the reason African Americans had the highest rate of vaccine uptake at the beginning but the lowest rate as time progressed in terms
of whether it was related more to access or lessening interest in the vaccine. Dr.
28

 Delaney noted that the AMETHYST questions could unpack that more, though intention
to get vaccine has not yet been assessed by race and ethnicity .
• It seems that more education is needed to make at risk populations aware of the
problem, given that the target populations do not know much about the vaccine and/or
Mpox disease. Dr. Delaney acknowledged that the AMETHYST and AMIS cohorts
showed that there were gaps in knowledge, so CDC adapted its messaging based on
those early survey results to be more sex -positive and to ensure that the vaccine was
being talked about as a sexual health intervention, because most of the places where
the vaccine was available outside of the health equity events were STI and PrEP clinics and HIV care sites. The Community Engagement Task Force developed the materials
and the social media marketing and worked with CDC’s community partners to get the
message out to the most affected communities. He agreed that more needs to be done.
• The difference between the number of people who are interested in the vaccine and the
number who actually have taken the vaccine is striking. That disconnect suggests that there is creative work to be done.
• One approach to address the equity issue is positive deviance; that is, highlight successes and figure out how to learn from them.
• From a local public health standpoint, the aspect of achieving equity is often a matter of having adequate resources for local public health and their partners to conduct effective outreach to those who are at higher risk. ACIP’s guidance and identification of potential
equity issues can help to direct resources accordingly .
• Equity always has been increased in terms of pediatric vaccines because of the
Vaccines for Children Program (VFC). Because there is not a comparable program for adult vaccines, barriers can increase equity among adult populations.
Following Dr. Carter’s Presentation
• The launch of this response was very difficult because the vaccine distribution system was totally different from what all of the public health immunization programs had been utilizing beforehand. In terms of the issue of equity, states were only allowed to have 5
sites receive vaccine. That is one of the reasons why there was such limited distribution
of the vaccine. If the SNS is going to be used via ASPR, consideration must be given to
the efficiency of that distribution system.
• This presentation highlighted the complexity of the response and how many people were involved, both on the frontline and behind the scenes. The data with doses by month addressed the equity issue and demonstrated clearly that the concerted efforts were
effective. All jurisdiction s should be encouraged to look at their data in a similar way .
• Immunization registry reporting is critical to determine what doses have been given and
to avoid errors.
• The lessons learned from Mpox should be applied to other outbreaks to inform quick mobil ization versus spending months gearing up for an unexpected outbreak.
• It would be nice to have an overall statement saying that ACIP does not recommend routine HCP vaccination for frontline workers, along with more guidance about when
PEP should be offered to frontline HCP who perhaps were not using personal protective
equipment (PPE) and later finds out a patient has Mpox.  Dr. Carter indicated that CDC
worked closely with its Healthcare Worker Task Force and NIOSH colleagues to review
this carefully and the conclusion was that PPE recommendations provided adequate
protection against the risk of Mpox transmission and therefore, JYNNEOS vaccine was
not recommended for HCP. Certainly, someone who is exposed to Mpox who was not
adequately protected could be off ered PEP.
29

  • It would be beneficial to continue to have the flexibility to offer either the intradermal or
subcutaneous route of administration, especially since intradermal can be stigmatizing.
Following Dr. Rao’s Presentation
• Looking at the entire picture, this is a common disease. Even now at its lowest, there are still 2 cases per week. That is higher than the number of cases per week in the past few
years, and there is a fairly high death rate. There is a very effective vaccine with good
data.
• It was observed that case counts also have decreased in many countries where no
vaccine is available. While vaccine is certainly playing a role, behavioral changes also
may be having an impact.
• Significant information is still lacking for immunocompromised patients. In general, it
seems that immunocompromised patients need additional doses. Perhaps during the
October ACIP meeting, consideration can be given to additional doses of JYNNEOS for
immunocompromised patients . Dr. Rao indicated that CDC is collaborating with other
partners to try to conduct some immunogenicity studies to better understand the role of
JYNNEOS for immunocompromised patients and plans to discuss this with the WG.
Clinicians on the WG have raised this concern for HIV, immunocompromised, t ransplant,
and other patients who have higher risk.
• Concern was expressed that having a risk -based recommendation could limit access, be
stigmatizing to some extent, and present inherent challenges for future Mpox outbreaks
or other infectious diseases wit h similar characteristics. While education will help, it will
not solve the problem to the extent that someone who is not aware they are at risk needs to be seen in a clinical setting and that their risk needs to be assessed. CDC and
the WG emphasized that the ICC explains that individuals should not have to explain
their rationale for wanting to be vaccinated and that there is a need for continual community engagement and education to keep Mpox in the public eye.
• It will be important for longer -term recommendations and the ICC to address booster
dosing, which will be part of the WG’s discussion after June 2023.
• The question often arises about whether someone who recovered from Mpox should be vaccinated, which the WG is not currently recommending because it is believed that
these individuals will have protection from their natural illness. There are booster studies
underway that will inform booster dosing recommendations in the coming years.
• There can be complicated political considerations in declaring an outbreak. The proposed recommendation language is broad and as such offers the flexibility to
implement more aggressive vaccination measures if state and local health departments
feel that is needed.
• It is impressive that over 90% accurate data were captured on race and ethnicity . It
would be great to capture that information and information on disabilities in all clinical
trials and other studies in order to inform and enhance access.
30

   Vote: Mpox Vaccine
Agam Rao, MD (CDC/NCEZID) displayed and read the proposed vote language following the
public comment period. The vote was combined with the Mpox session for ease of reading :
ACIP recommends the2- dose* JYNNEOS vaccine series for persons aged 18 years and
older at risk of Mpox during an Mpox outbreak? §
*Dose 2 administered 1 month after Dose 1
§Public health authorities will determine whether there is an Mpox outbreak; a single case may be considered an Mpox
outbreak at the discretion of public health authorities. Other circumstances in which a public health response may be indicated include ongoing risk of introduction of Mpox into a community due to disease activity in another geographic area.
Motion/Vote: Mpox Vaccine
Dr. Loehr made a motion to approve the recommendation as stated, which Dr. Poehling
seconded. No COIs were declared. The motion carried with 14 affirmative votes, 0 negative
votes, and 0 abstentions. The disposition of the vote was as follows:
14 Favored: Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long, McNally,
Poehling, Sanchez, Talbot
0 Opposed: N/A
0 Abstained: N/A
RESPIRATORY DISEASE SURGE, FALL 2022, UNITED STATES
José R. Romero, MD (CDC, Director NCIRD) emphasized that it was a pleasure to speak to
ACIP in his role as Director of NCIRD. Having previously served as a member and the C hair of
the CDC’s ACIP, he truly understands and greatly appreciate s the time and effort required by its
members to convene a meeting of the ACIP. He observed that o ver the course of the meeting,
the committee would hear presentations on influenza and COVID -19 vaccines , as well as novel
RSV vaccines. To set the scene for the next few sessions, he wanted to give a brief overview of
the co -circulating respiratory viruses that are observed over the W inter and F all and highlight
how they are of critical importance in terms of vaccination. This past Fall and Winter, the US
saw high co- circulation of respiratory syncytial virus (RSV), influenza virus, and SARS -CoV-2.
Thes e put significant stress on healthcare systems and the drug supply chain. After a brief and
anticipated uptick of hospitalizations and cases around the holidays, there is now a continued
decrease in COVID, influenza, and RSV cases and hospitalizations nati onally.
For those who are not pediatricians, he explained that RSV is a well- recognized respiratory
pathogen of infants and a common cause of respiratory disease in older adults. In adults, RSV
can be difficult to differentiate from COVID -19 and influenza based on symptoms alone and is
frequently overlooked as a diagnosis for viral respiratory disease in adults. In the elderly or in
those with certain comorbid conditions, RSV infections can be significant and life- threatening.
Typically, adults experience mild cold- like symptoms, although some can develop a lower
respiratory tract infection (LRTI) such as pneumonia. Older adults, adults with chronic heart and
lung conditions or diseases , and those with weakened immune systems are at higher risk for
31

  severe RSV infections. RSV is also known to lead to worsening of chronic conditions common in
adults, such as asthma, congestive heart failure, and chronic obstructive pulmonary disease
(COPD) . Each year in the US , it is estimated that between 60,000 and 160,000 hospitalizations
occur and 6 to 10,000 deaths result in older adults due to RSV infections. This past fall, the
CDC surveillance team saw an increase in RSV detections, RSV -associated emergency room
department visits , and hospitalizations, including among older adults. Current national trends for
RSV activity indicate that it has returned to baseline levels. For seasonal influenza, the activity
continues to decline across the country. While influenza activity is declining, it remains possible
that a second wave may occur later in the season as it has in the past.
CDC has responded to the increase in co- circulating respiratory viruses in multiple ways, but Dr.
Romero thought the most important way to bring before the ACIP was that in January 2023,
CDC released 2 new respiratory diseases surveillance dashboards that are accessible to public
health medical professionals and the public in general. The first is th e Respiratory Virus
Hospitalization Surveillance Network (RESP- NET), which is an interactive dashboard that
displays respiratory virus -associated hospitalizations from 3 existing surveillance platforms :
Coronavirus Disease 2019 (COVID- 19) Hospitalization Surveillance Network (COVID -NET) ,
Influenza Hospitalization Surveillance Network (FluSurv -NET) , and Respiratory Syncytial Virus
Hospitalization Surveillance Network (RSV-NET). The second dashboard is the National
Emergency Department Visits for COVID -19, Influenza, and Respiratory Syncytial Virus, which
displays data on emergency room visits for multiple respiratory conditions as tracked by the
National Syndromic Surveillance Program (NSSP). This dashboard presents data captured from
approximately 75% of all emergency departments (EDs) in the US , so it is a very robust
database. These dashboards allow users to easily see hospitalizations and ED data for these 3
viruses by age and track and compare the trends for SARS -CoV-2, influenza, and RSV disease.
Recent outbreaks highlight the importance of remaining vigilant about prevention. CDC
continues to conduct outreach to clinicians, public health, and school partners and the public to
raise awareness about the importance of vaccination for COVID -19 and influenza for everyone
6 months of age and older. Dr. Romero noted that during the first day of this meeting, there
would be presentations and discussion on pediatric and maternal RSV vaccines that may
become available for the prevention of RSV -related disease in the near future. Since the
detection of the first case of SARS -CoV-2 virus over 3 years ago, more than 1 million
Americans, including 2,000 children, have tragically died as a result of COVID -19 infection.
Nearly 6 million individuals have been hospitalized and many more continue to suffer from long-
COVID conditions. Fortunately, due t o the rapid development of safe and effective vaccines, the
position is very different from 3 years ago. COVID -19 vaccinations have prevented millions of
severe illnesses, hospitalizations, and deaths since their introduction in December 2020. Many current members of the ACIP were on the committee at that time. Now 80% of Americans have
received at least 1 dose of the primary COVID -19 vaccine series and over 667 million doses of
vaccine have been administered. However, despite the introduction of a bivalent booster in
September 2022 , uptake has been low with only 15% of the US population having received an
updated booster. The numbers are even lower for pediatric patients. Vaccinations and antivirals
continue to be the best protection against serious illness for COVID -19.
32

  Unfortunately, during the COVID -19 pandemic, there was a concerning decrease in routine
immunizations for both adults and children. Routine vaccinations are rebounding, although
unevenly , and have yet to fully recover in all groups. A significant and extremely concerning
example is that the percentage of uninsured children not vaccinated by their second birthday
was recently found to be 8 times that of privately insured children. That is even in the context of
VFC, a program that is designed to address these inequities in healthcare insurance. While
continuing to investigate the impact of the pandemic on routine immunizations, it is imperative to
take steps to help get everyone back on track with their routine immunizations. Everyone must
continue to work together to improve vaccination coverage by reduc ing barriers, increas ing
access, and strengthening vaccine confidence. For influenza and COVID- 19, safe , effective,
licensed or authorized vaccines are currently available for the prevention of serious disease. It is
very possible that in the not-too-distant future , Americans also may have options for the
prevention of a third respiratory virus, RSV. With that, Dr. Romero thanked ACIP and wished
them good luck with t heir deliberations and discussions.
Discussion Points
Before opening the floor for discussion, Dr. Lee emphasized Dr. Romero ’s key points. First,
context is everything. Many f amilies with children and/ or older adult members have had multiple
respiratory viral illnesses this Winter. On top of that, pediatric providers had such a significant
respiratory surge during a certain period of time, all due to multiple respiratory illness es, they
had to divert and redirect many of the children who were very ill and needed care. There also
were other children who needed to come in for other reasons. This has had a major impact on
the healthcare delivery system and families. One reason the ACIP was so grateful to Dr.
Romero for being willing to speak about this context was that for the first time in a long time,
ACIP had the opportunity during this meeting to review data on influenza vaccines, RSV ,
COVID -19, and pneumococcal vaccines. All of those are important preventive measures for
ACIP to consider as part of a potential respiratory disease prevention platform. While they would
take each of these vaccines into consideration on an individual basis, it also is important to think
through the broader implementation context for young children and older adults to ensure that
as the committee is m aking these recommendations, they also are thinking ahead about how
these programs would be deployed in the various populations.
In response to Dr. Loehr ’s request to speak further to Dr. Romero’s revelation that the
percentage of uninsured children not vaccinated by their second birthday was recently found to
be 8 times that of privately insured children , Dr. Romero said that given that the VFC was in
place and functioning well pre- pandemic, this suggests a major problem. The VFC was
established to address barriers in access, yet this problem of lower vaccine rates has been particularly severe among racial and ethnic populations, rural areas, and areas experiencing
poverty.
Dr. Talbot expressed excitement about viral vaccines coming online for older adults , but
lamented how complicated vaccines are for adults over 65 years of age because of Medicare.
She asked whether any processes are in the work s to streamline vaccines under Medicare Part
B so that physicians can vaccines while patients are in the clinic .
Dr. Wharton indicated that there have been some changes in policy with recent legislation. She
called upon Mary Beth Hance to make some brief co mments about the changes to Medicare
vaccine reimbursement issues under Medicare Part B and D from the Inflation Reduction Act
(IRA).
33

  Mary Beth Hance (HRSA) indicated that the IRA made changes to coverage of vaccines for
adults in Medicare . COVID -19 was added as a Part B covered vaccine. For P art D, there is no
cost sharing for patients . Covered Part B vaccines now include influenza , pneumococcal,
hepatitis B for individuals at high and intermediate risk , COVID -19 vaccines , and vaccines that
are reasonable and necessary to treat an injury or exposure to a disease. There is coverage of
ACIP -recommended vaccines with no cost -sharing under Part D .
Dr. Romero added that while this benefit s those with insurance, there is still a large population
of adults in the US who do not have insurance. Serious consideration of a program that would
offer vaccine to those individuals, a Vaccines for Adults (V FA) modelled in some way after the
VFC, is something the American public needs to consider moving forwar d in order to catch all
Americans up on vaccinations and make these vaccinations available to all.
Dr. Daley asked what is known about vaccination rates for adults without insurance and if there
is a comparable figure for influenza or COVID vaccination, a nd what would be required to
establish a VFA program.
Dr. Romero indicated that he could share specific data during the Agency Update session, but
that rates are substantially lower for those who are uninsured. Even a co -pay can be a deterrent
to accessin g vaccines. Establishment of a VFA would need to be appropriated for within the
President ’s Budget and legislated by Congress.
Dr. Goldman (ACP) asked whether it would be within CDC’s purview to handle certain state
jurisdictions deliberately spreading disinformation regarding the safety and efficacy of the
vaccines .
Dr. Romero responded that CDC, as always, is engaged with educating the public and providing information that is scientifically correct and sound. It is not within the realm of C DC to actively
involve itself within jurisdictions. Simply put, these are decisions made by the jurisdiction or
jurisdictions involved.
Dr. Hogue (APhA) said he was struck by the inequities that still exist in US society and
emphasized that they should all do what they could to address them. He reported that America's
pharmacies are having significant issues with the Part D plans and the inconsistency with which
the Part D plans cover the administration of vaccines. They treat vaccines as drugs because
they have a National Drug Code ( NDC) number, but many of the Part D plans either try to
bundle the administration fee with the vaccine for administration simplification or they pay very
little or no administration fee at all. His concern is that during the pandemic , people have
become quite dependent upon community -based pharmacies to improve access points,
especially in rural areas of the country. If the Part D plans are not held to account by CMS to
consistently pay a meaningful administration fee and stop clawback s, which are very common in
the pharmacy world for drugs, it could result in a situation of pharmacies being unable to offer
vaccines for Medicare beneficiaries under the Part D plan in the future. Therefore, he wanted to
raise this awareness and an alarm bell so that colleagues at CMS would work with them to try to
correct this situation in the coming Part D Call Letter.
34

  INFLUENZA VACCINE
Introduction
H. Keipp Talbot, MD, MPH (ACIP, WG Chair) indicated that this session would include
presentations focused on influenza activity, interim influenza VE against inpatient, ED, and
outpatient illness in the 2022- 2023 season, interim estimates of 2022- 2023 influenza VE from 2
studies in Wisconsin, and published estimates of live attenuated influenza vaccine (LAIV).
US Influenza Activity Update
Lisa Grohskopf MD, MPH (CDC/NCIRD) presented a brief update of the 2022- 2023 US
influenza activity. In terms of virological surveillance data, results of influenza -positive tests are
reported weekly to CDC from a very large network of clinical and public health laboratories. The
percent of positive influenza tests is one of the indices of influenza activity. For 2022 -2023, the
percent of positive tests peaked in late November /early December at about 26%. The percent
positive has been decreasing for about the 9th consecutive week to 1.7%. The peak of 26% is
roughly comparable to other recent seasons. However, the peak shifted earlier than is typical.
The peak also was higher than the 2 seasons immediately preceding 2022- 2023. The other
component of this system, Public Health Laboratories (PHLs), provides a sense of the influenza viral types and subtypes in circulation. H3N2 viruses have predominated, although there also
has been appreciable co -circulation of H1N1pdm09- like viruses. About 99.4% of the viruses
characterized thus far have been influenza A. Very little influenza B has been seen at this point in the season.
Laboratory -confirmed influenza- associated hospitalizations come from FluSurv -NET.
Cumulative hospitalizations have leveled off at about 59.5 per 100,000 and have stayed flat in
recent weeks. As with the peak shift, influenza -associated hospitalization activity shifted earlier
in the season as well. Deaths of children associated with laboratory -confirmed influenza has
been reportable in the US since 2004. Thus far, as of the weekend ending February 11, 2023, a
total of 1 11 pediatric deaths have been reported through the Fluview mechanism. This is
unfortunately more than in 2020- 2021, for which 1 pediatric death was reported and 2021 -2022,
for which 45 pediatric deaths were reported.
To summarize influenza activity as of the week ending February 11, 2023, US influenza act ivity
rose early, peaking nationally during late November/early December. The percent that test ed
positive peaked at about 26% and is currently down to about 1.7%. Influenza A (H3N2 ) virus has
predominated so far with co- circulation of A(H1NI )pdm09. The cum ulative influenza- associated
hospitalization rate has leveled in recent weeks to about 59 per 100,000. A total of 111
influenza- associated pediatric deaths have been reported thus far this season. Overall influenza
activity is increased compared with the previous 2 seasons. US influenza activity is currently
low.
35

  Preliminary 2022 -2023 Influenza Vaccine Effectiveness: CDC Networks
Samantha Olson, MPH; Nathaniel Lewis, PhD; and Mark Tenforde, MD, PhD (CDC/NCIRD)
presented preliminary 2022- 2023 influenza VE results from 3 CDC networks: New Vaccine
Surveillance Network (NVSN), Investigating Respiratory Viruses in the Acutely Ill (IVY), and the
VISION Vaccine Effectiveness Network . Ms. Olson explained that CDC uses these 3 networks
to evaluate VE against laboratory -confirmed influenza- associated outpatient visits, emergency
department visits, and hospitalization. Across all 3 networks, the methods are similar. For this
analysis, patients were enrolled with acute respi ratory illness (ARI) from Fall 2022 through early
2023. Each study has a test -negative design comparing vaccination odds among case patients
with influenza A confirmed by molecular assay versus control patients testing negative for
influenza and SARS- CoV-2. Vaccination status was defined as the receipt of any 2022 through
2023 influenza vaccine according to medical records, immunization registries, claims data,
and/or a self -report. For each analysis, VE was calculated as (1 ─ the adjusted odds ratio) x
100.
The NVSN analysis calculated VE against influenza- associated hospitalizations and ED visits
among children 6 months through 17 years of age. NVSN conducts active surveillance at 7 sites
across the country: Seattle Children’s, Children’s Mercy Hospital Kansas City, Texas Children’s
Hospital Houston, Vanderbilt University Nashville, Cincinnati Children’s, University of Rochester,
and Children’s Hospital of Pittsburgh. NVSN enrolled inpatient and ED patients 6 months
through 17 years of age with acute respi ratory illness within 10 days of illness onset from
September 13─January 25 for this analysis . A test-negative design was used in which patients
were considered vaccinated if they received at least 1 dose regardless of their age and relied on
verified vaccination or self -report. Logistic regression was used for this analysis, adjusting for
site, age, and calendar time of admission.
In terms of preliminary VE estimates against pediatric hospitalizations and emergency
department visits among children 6 months through 17 years of age. T here were 640 influenza-
positive cases and 2,256 controls included in this analysis. Nineteen percent of cases versus
33% of controls received a seasonal influenza vaccine. O verall VE was 49% among inpatients,
with a higher -point estimate of 68% observed . Among ED visits, 42% VE was calculated.  When
stratified by subtype, effectiveness against H3N2 was 45% and against H1N1 was 56%. To
summarize, b ased on preliminary estimates for the 2022─2023 influenza season, influenza
vaccinations significantly reduced laboratory -confirmed medically -attended influenza in children.
Effectiveness against pediatric hospitalizations was 68%. Effectiveness against pediatric ED
visits was 42%, and important protection was observed against both H3N2- and H1N1-
associated illness. Dr. Lewis explained that the IVY analysis assessed VE against influenza- associated
hospitalization among adults ≥18 years of age receiving inpatient medically -attended treatment
for influenza. This analysis was drawn specifically from patients at 24 medical centers in 19
states in the IVY network shown in the map below:
36

The methods used in IVY are very similar to the NVSN methods. The data rage for the analysis
was October 1─January 31, 2023. This analysis used a test -negative case -control method that
assessed the odds of vaccination among cases versus controls . This analysis was adjusted for
Census region, age, sex, race /ethnicity, and month of illness onset. Fairly encouraging results
were s een in this analysis of 219 cases who tested positive for influenza and 921 controls who
tested negative for both influenza and SARS -CoV-2. Vaccination coverage was 31% among
cases and 43% among controls. Overall, VE was 43% for persons ≥18 years of age. As
expected, there was some variation by age group , with lower protection among those ≥65 years
and older of 35% versus 51% among those 18─ 64 years of age . Importantly, significant
protection was observed in the immunocompromised subgroup that was very similar to that of
overall VE in the network , albeit with a wider and overlapping confidence interval. About two -
thirds of the 77 specimens analyzed through the end of 2022 were H3N2 and the remaining
third were H1N1. The important takeaway is that influenza vaccination significantly reduced
medically -attended hospitalized influenza at a VE of 43% . Significant protection was observed in
the older adult population and among immunocompromised adults.
Dr. Tenforde present ed preliminary results from the VISION network on influenza VE results
against influenza- associated hospitalizations and ED or urgent care (UC) visits. VISION is an
electronic VE network that consists of health systems with integrated laboratory , clinical, and
vaccination records. The 3 partners contributed data for this analysis, including Kaiser
Permanente Northern California (KPNC) , Intermountain Healthcare, and HealthPartners in 4
states. For this analysis , encounters included ED or UC visits or hospitalizations between
October 15 ─January 24, 2023 among adults ≥18 years of age w ho received clinical testing for
influenza and had 1 or more ARI -associated discharge codes. Using a test-negative design, VE
was estimated by comparing influenza vaccination odds among patients who tested positive for
influenza A versus controls who tested negative for influenza and SARS- CoV-2. VE models
applied inverse- propensity -to-be-vaccinated weights and adjust ed for potential confounders
including patient age, study site, and calendar time. Preliminary VE estimates against adult ED or UC visits were calculated for 14,011 influenza -
positive cases and 43,196 influenza- negative controls included in t his analysis. Twenty -three
percent of cases versus 36% of controls had received a 2022- 2023 seasonal influenza vaccine.
Overall VE was 44% in all adults ≥18 years of age, including 46% in adults 18─64 years and
39% in adults ≥65 years of age. A lower point estimate of 30% was seen among adults with
immunocompromising conditions. In terms of VE estimates against adult hospitalizations , the
analysis included 1,760 influenza- positive cases and 9,377 influenza- negative controls. Thirty -
37

      eight percent of cases versus 49% of controls had received a seasonal influenza vaccine.
Overall VE was 39% , including 29% in adults 18─ 64 years of age and 42% in adults ≥65 years
of age . VE was 31% among adults with immunocompromising conditions.
In summary, through almost the end of January 2023, influenza vaccinations significantly reduced laboratory -confirmed medically -attended influenza with an estimated VE of 39%
against adult hospitalizations and 44% against adult ED or UC visits. Effectiveness was
observed across all age groups and in those with immunocompromising conditions. These
estimates were higher than VISION Network VE estimates against hospitalization and ED or UC
visits from the same sites during the prior 2021-2022 season when mostly vaccine mismatched
H3N2 v iruses were circulating. A limitation of this analysis was a lack of data to estimate VE by
influenza A subtype including H1 and H3 viruses.
In conclusion, across 3 influenza VE platforms, very consistent influenza VE was observed
during the early 2022- 2023 influenza season. Vaccination provided substantial protection
against inpatient ED and outpatient illness across all ages. Influenza vaccination also provided
substantial protection among important high- risk groups , including older adults and those with
immunocompromising conditions.
Preliminary 2022 -2023 Influenza Vaccine Effectiveness: Wisconsin
Huong McLean PhD, MPH (Marshfield Clinic Research Institute) presenting interim
estimates of influenza VE from 2 studies in Wisconsin: A test- negative case-control study
funded by CSL Seqirus and a community cohort study funded by CDC. The methods of the test -
negative case -control study are similar to what was presented for the 3 CDC networks , except
that the enrollees are outpatients who presented for COVID -19 testing aged 6 months through
64 years with ARI with a cough of ≤7 days duration. Data presented are from enrollments from
December 2, 2022 through February 10, 2023. Influenza vaccination was defined as
documentation in the patient ’s health record of current season influenza vaccine receipt ≥14
days before illness onset according to the ACIP recommendations. VE estimates were adjusted
for age, month of illness onset, and presence of high- risk co nditions.
Influenza positive RT -PCR results were highest at the beginning of the enrollment period in
December and have declined since. Of the viruses, 73% were A(H3N2 ) and 26%
A(H1N1pdm09). All of the 43 characterized viruses were genetically similar to the vaccine
components. A total of 545 patients with medically -attended ARI were included in this analysis.
Among participants, 34% were vaccinated , of whom the majority (84%) received cell-culture
based vaccine (ccIIV4). The percentage vaccinated differed by sex, high-risk conditions, and
COVID -19 vaccination status. Among the 116 participants positive for influenza, 22% were
vaccinated compared to 37% of 429 participants who tested negative for influenza and SARS -
CoV-2. The adjusted VE against outpatient medically -attended influenza A was 54% , with a
95% confidence interval of 23 % to 73%. VE against influenza A(H3N2 ) viruses was 60% , with a
95% confidence interval of 25% to 79%.
The prospective community cohort study is an ongoing study in Central Wisconsin of 241
children who have been followed weekly since September 5, 2022. Each week, children or their
guardians report the absence or presence of the following symptoms over the past 7 days :
fever, cough, loss of smell or taste, sore throat, muscle or body aches, shortness of breath,
diarrhea, nasal congestion or runny nose, or nausea or vomiting. New symptom onset prompts
self-or guardian- collection of anterior nasal swab for influenza and SARS- CoV-2 research
testing. Other relevant information collected from surveys and extracted from EHRs includ e
38

  vaccination history and clinic influenza test results. To estimate VE against symptomatic
influenza infection in the cohort, a Cox proportional hazards model was used with time -varying
vaccination st atus. The at -risk window began October 23 , 2022 (7 days before the first case
was identified) and ended February 10 , 2023 (positive influenza infection date)—whichever
occurred first. Vaccinated person time began ≥14 days after receipt of the influenza vaccine.
Unvaccinated person- time was the time before receipt of influenza vaccine. P erson- time was
censored for the 13 days after receipt of influenza vaccine. An influenza case was defined as a
positive influenza result from a research or clinical test during the at-risk period. V E
effectiveness was calculated as 1 minus the adjusted hazards ratio x 100% where the hazards
ratios represented the ratio of influenza infections in the vaccinated to unvaccinated person-
time. The model adjusted for age, higher at -risk condition, and COVID -19 vacation. Among the
241 children in the cohort, 39% were vaccinated , of whom 84% received ccIIV4 and 65%
received 2 or more doses of COVID -19 vaccine. A total of 34 (14%) of children were positive for
influenza.
In terms of influenza and SARS- CoV-2 infections by week of onset , influenza incidence was
highest late November and early December and has declined since. Of the influenza infections,
85% were caused by A(H3N2 ), 3% were caused by A( H1N1 pdm09) , and the remai ning 12%
were influenza A with unknown subtype. The characterized A(H3N2 ) viruses in this population
were genetically similar to the vaccine component. Regarding VE against symptomatic influenza
among children, there were 6 influenza A infections during the 7,292 vaccinated person days of
follow- up, resulting in an incidence of 0.82 infections per 1,000 person- days. A total of 28 cases
occurred during the 15,678 unvaccinated person- days , resulting in an incidence of 1.79
infections per 1,000 person days. VE against symptomatic influenza A virus infection was 71%
with a 95% confidence interval in 31% to 90% among children in this cohort.
There are several limitations to consider for these studies. First, both studies were conducted in
a single geographic area, Central Wisconsin. However, the virus es that predominated in the
study population was similar to those that predominated across the US. Second, adults ≥65
years of age who generally have lower VE estimates against A(H3N2 ) were excluded. Third, the
sample sizes were small. This resulted in wide confidence intervals, so it was not possible to estimate VE against A(H1N1 pdm09) or by age groups. Finally, confounding and bias are
concerns with observational studies. However, estimates were comparable across the 2 study
designs.
To summarize, interim results indicate substantial vaccine- induced protection against influenza
A during the current season. VE effectiveness was 54% against medically -attended influenza A
in children and working- age adults and 71% against symptomatic influenza A infection in
children. These estimates are consistent with reported estimates from the 4 CDC networks and
in Canada and are consistent with a good vaccine match. All characterized viruses from the
study population belong to the same genetic subclade as the viruses included in the 2022- 2023
Northern Hemisphere influenza vaccine.
Update on Published Estimates of LAIV4 Effectiveness: Background
Lisa Grohskopf MD, MPH (CDC/NCIRD) presented a brief update of published estimates of
live attenuated influenza vaccine ( LAIV ) effectiveness, noting that these are not CDC data.
LAIV4, the quadrivalent LAIV, was initially approved in the US in 2012 and came into use during
the 2013 -2014 season after having had a trivalent formation available since 2003 in the US.
LAIV4 was not recommended in the US for use during the 2016- 2017 and 2017- 2018 seasons
following observation of low effectiveness specifically against H1N1pdm09 -like viruses among
39

  children 2─17 years of age that was noticed during the 2013- 2014 season and during the 2015 -
2016 season, both of which had some H1N1 predominance. It was not clear what was going on
when this first was noticed. The 2013- 2014 season was the first H1N1 -predominant season that
had occurred since the 2009 influenza pandemic.  It also was the first season the quadrivalent
product was available. However, subsequent studies suggested decreased replicat ive fitness of
the LAIV4 H1N1pdm09 -like vaccine virus . Live virus vaccine such as this requires replication of
the virus in the nasopharyngeal mucosa in order to be effective. Following those studies, the
vaccine virus was updated and replaced in the vaccine. LAIV4 was again a recommended
option in the US starting in 2018- 2019 after a discussion of 3 streams of data during the
February 2018 ACIP meeting. These included a combined US individual patient level VE analysis that consisted of data from several US sources , a systematic review of post -2009 US
and non- US LAIV VE estimates, and MedImmune data on the new H1N1pdm09- like vaccine
virus that indicated a better immunogenicity and fitness of that new virus.
Unfortunately, subsequently LAIV4 use within the CDC US VE networks has been low since the
2018- 2019 season, which has precluded assessment of vaccine- specific VE in the US from
these networks. However, LAIV VE estimates have been published from non- US observational
studies.
16 For comparison, an effort was made to pool from the same papers where available,
either IIV inactivated vaccine quadrivalent VE estimates, or if such were not available, estimates
for all vaccines. These estimates are all for children for whom the age groups vary somewhat ,
given that they represent the age groups for whom vaccine was licensed. Starting with Finland
for 2018- 2019 , LAIV4 VE estimate for children 2─6 years of age was 36% and VE for IIV4 for
children 6 months─6 years of age was 54%. For UK, 2018- 2019 VE for LAIV VE was 49% for
children 2─17 years of age and 53% for all vaccines in this same age group. For 2019 -2020,
estimated LAIV4 VE of 45% was reported in the UK for children 2─17 years of age. For 2021 -
2022, estimated LAIV4 VE of 72% was reported in the UK fo r children 2─17 years of age. For
2021- 2022 in Denmark, VE for all vaccines among non- hospitalized children 2─6 years of age
was 64% and was 63% for hospitalized children of the same age. This paper notes that these
children were offered LAIV4, which 92% received. Others received inactivated vaccine, so these
are predominantly LAIV4 estimates .
ACIP Discussion Points, Observations, Suggestions on Influenza Vaccine
Following Dr. Grohskopf ’s First Presentation
• Regarding questions about whether the pattern of the 111 pediatric death cases was
similar to prior years with 50% having no co- morbidities, Dr. Grohskopf indicated this
was not yet known for this season. It takes a while for this information to come in, but the
50% that was published in a 2018 paper from her group is fairly typical.
• In terms of questions about why influenza began and peaked so early this season, Dr. Grohskopf noted that influenza seasons are unpredictable, and this is not the first time
an early influenza season has occurred. She referred to a chart on the CDC webpage
that covers about 39 influenza seasons to date that shows a couple of seasons that peaked as early as October .
• The hospitalization rate seems somewhat low despite the brisk influenza season, which raised questions about whether this was due to better diagnostics and therapeutics
and/or better recognition of viral disease. Dr. Grohskopf indicated that this cannot be
discerned form the type of data that come from that system, but it is certainly plausible to
16 A) Stuurman et al Vaccine 2020;38:6455- 64632; B) Pebody, Vaccine 38 (2020) 489–4; C) Stuurman et al Vaccine 2021;39:3964-
3973; D) https://webarchive.nationalarchives.gov.uk/ukgwa/20220401215804/https://www.gov.uk/government/statistics/annual -flu-
reports ; E) https://www.gov.uk/government/statistics/annual -flu-reports/surveillance- of-influenza- and-other- seasonal -respiratory -
viruses -in-winter- 2021- to-2022 ; and F) Emborg, Euro Surveill2022;27:pii=2200278
40

  think that people have a lower index of wanting to get checked by a medical provider
given all that everyone has been through over the last couple of years. Certainly,
influenza seasons vary in severity. H3N2 seasons are generally more severe than
H1N1, and there appears to be a reasonably good vaccine match.
Following Presentations by Ms. Olson, Dr. Lewis, and Dr. Tenforde
• Regarding an inquiry about what percentage of persons ≥65 years of age in the IVY and
VISIONS studies received the preferentially recommend high- dose vaccine, Dr.
Tenforde indicated that most persons 18─64 years of age received standard- dose
inactivated quadrivalent vaccines and the majority (90%) of individuals ≥65 years of age
received either a high- dose vaccine or adjuvanted vaccine product. Dr. Lewis added that
while they are awaiting more complete product data for IVY, the breakdown in the past has been similar with the majority of persons 18─64 years of age receiv ing standard-
dose inactivated quadrivalent vaccines and the majority (90%) of individuals ≥65 years
of age receiving some type of enhanced vaccine product.
• With regard to an inquiry about how many children received LAIV, Ms. Olson indicated that LAIV uptake has been low within the NVSN Network facilities.
• In terms of why SARS- CoV-2 was excluded from the analyses and if that changed the
comparisons to past years, Dr. Tenforde indicated that patients had to be negative for
influenza and SARS- CoV-2 to be part of this analysis. Most patients who received
influenza testing also received testing for SARS -CoV-2. The reason they were excluded
as controls was because there is a potential for a confounding relationship where receipt
of influenza vaccination is correlated with receipt of COVID -19 vaccination. Essentially ,
controls can be enriched with patients who had COVID -19 and potentially bias VE
estimates.
• It is important to highlight that among the pediatric deaths, only about 22% were fully vaccinated with 2 doses.
• With respect to whether the WG is aware of any new influenza vaccines on the horizon with less disappointing efficacy, Dr. Talbot pointed out that everyone would like to find
the Holy Grail. A unique aspect of influenza infection in adults is that adults have been
exposed to RSV and influenza many times in their lives. Yet, the vaccine is still being
expected to do something that the human immune system has not figured out. There are
multiple components to this , including the aging immune system , the changing virus, and
the vaccines primarily induce a B- cell response. There is some T- cell response, but
there is very little internal protein in current vaccines that would stimulate the T- cells.
While many scientists including herself are looking for a universal influenza vaccine, they still have the vaccine that was developed originally for military recruits. It is somewhat
cleaner and less reactogenic than it was when it was first discovered, and it still prevent s
a fair number of hospitalizations and deaths each year. Therefore, it will continue to be
used until the Holy Grail appears.
Following Dr. McClean’s Presentation
• The prospective cohort study is intriguing. The incidence per 1,000 person -days of 0.82
for the vaccinated and 1.79 for unvaccinated persons results in approximately 1 per
1,000 person days. Based on a 3- month influenza season, the number needed to
vaccinate (NNV) would be 10 people to prevent 1 illness.
• Notably, the test -negative case- control study began in December and likely missed
some cases due to the early start of the influenza season.
41

        Following Dr. Grohskopf ’s Second Presentation
• Notably, the measures , definitions , and criteria vary in the non-US studies. Dr.
Grohskopf emphasized that some variations are expected because there are variations
in matches from season- to-season and in methods, especially among observational
studies.
• There appears to be a theme that this vaccine is unlike Coronavirus vaccine in that it
does not seem to protect better against worse outcomes. It may be somewhat different
for ARI and hospitalization, but not as dramatically. It was not clear whether this was real or the way that people are being investigated. Dr. Grohskopf said that to be comple tely
honest, she was not sure. Much of the data she is familiar with on prevention of severe
outcomes focuses more on influenza vaccines broadly, while she was less familiar with
the specifics on LAIV. She will look this up and provide a response at a later time.
• One of the major challenges that will need to be addressed is that because people are able to test themselves at home, they may be less likely to go to their doctor. Those who
do present to medical settings are getting multiplex testing. As more point -of-care
diagnostics move into the home setting, consideration will have to be given to how
meaningful surveillance can continue to be conducted in that context. These data are
needed in order to continue to ensure the benefit -risk balance of prevention programs .
• It would be beneficial to include LAIV information in any publications regarding VE, given
that many parents have questions and would like to see these data.
PNEUMOCOCCAL VACCINES
Introduction
Katherine A. Poehling, MD, MPH (ACIP WG Chair) reminded everyone that pneumococcal
vaccines currently recommended for use in the US include PCV13 and PCV20 for adults .
PCV13 and  PCV15 are recommended for children . PPSV3 has a risk -based recommendation
for children. PPSV3 is recommended for adults who previously received PCV13 or PCV15, but
not for those receiving PCV20 20. The goal is to move forward with fewer differences. As a
reminder, all children under 2 years of age have the same pneumococcal vaccine
recommendation for 3 primary series and a booster, often known as the 3 + 1 schedule. The
primary series doses are administered at 2, 4, and 6 months and the booster is given at 12 to 15
months later. Currently, either PCV13 or PCV15 can be given to US children. Children with
certain underlying conditions are recommended to receive PPSV23 . Children with chronic
medical conditions (CMC), cerebrospinal fluid (CSF) leak, and cochlear implants are
recommended to receive PPSV23 ≥8 weeks after the conjugate vaccine. Children with
immunocompromising conditions are recommended to receive PPSV23 ≥8 weeks after the
conjugate vaccine. Then ≥5 years later , a second dose of PPSV23 is recommended . Children
6─8 years of age with CMC can receive PPSV23 if they did not receive pneumococcal
conjugate vaccine. Of note, CMC includes chronic heart disease (CHD), chronic lung disease
(CLD),and diabetes mellitus (DM) .
Approval of PVC20 use among children is anticipated later this year. It is anticipated that later in
Quarter 2 of 2023 , pediatric PCV20 will be approved. Pediatric PCV15 use was approved in
June 2022. With that in mind, the WG is considering the following policy questions:
Should PCV20 be recommended as an option for pneumococcal conjugate vaccination
according to currently recommended dosing and schedules for US children aged <2 years ?
42

 Should PCV20 without PPSV23 be recommended as an option for pneumococc al
v
accination for US children aged 2 ─18 years of age with underlying medical conditions tha t
i
ncrease the risk of pneumoc occal diseas e?
P
resentations during this session focused on the epidemiology of pneumococcal disease
among US children, pediatric outpatient ARI visits and antibiotic use attributable to serotypes in
higher valency pneumococcal conjugate vaccines, PCV20 P hase 2/ 3 study results among
children, preliminary E tR for PCV20 use in children, and WG considerations and next steps.
Epidemiology of Pneumococcal Disease among US Children
Ryan Gierke, MPH (CDC/NCIRD) presented an update on the current epidemiology of pediatric
pneumococcal disease in the US , beginning with a background on the spectrum of
pneumococcal disease. Pneumococcus is transmitted through airborne droplets from person -to-
person. It can colonize i n the nas opharynx and can be spread locally to the ears to cause otitis
media. It also can be aspirated and cause pneumonia. Pneumococcus also can infect the blood
and cause septicemia. These different infections can be characterized as either noninvasive
disease or invasive disease. Invasive pneumococcal disease (IPD) is a less frequent but severe
form of the illness. Noninvasive disease is more frequent . In children, otitis media is one of the
most common forms of pneumococcal disease. Note that pneumococ cal pneumonia can be
either invasive or noninvasive, depending on whether a sterile body site like blood becomes
infected in addition to the lungs. This presentation focused on: 1) IPD data in terms of the impact of pneumococcal conjugate
vaccines (PCVs ) and IPD incidence and serotype distribution; IPD incidence caused by
serotypes covered in the new conjugate vaccines, PCV15 and PCV20; and changes in IPD
incidence and serotype distribution resulting from the COVID -19 pandemic ; 2) the impact of
PCV13 on acute otitis media (AOM) and incidence estimates; and 3) the impact of PCV13 on
all-cause and pneumococcal pneumonia in children and recent estimates of pneumonia
incidence.
In terms of the impact of pneumococcal conjugate vaccines on pediatric IPD incidence and
serotype distribution among children in the US, data on IPD are obtained from the Active
Bacterial Core (ABCs) s urveillance system, which provides population- based surveillance at 10
sites across the US. Those are defined as pneumococcus -isolated from a normally sterile site in
residents of the 10 surveillance areas shown in the map below:
43

 Isolates are serotyped at reference laboratories using whole- genome sequencing (WGS) ,
Quellung, or PCR at reference laboratories . For analysis purposes, serotypes are grouped by
vaccine types. US Census Bureau estimates were used as denominators to calculate incidence
rates for overall and serotype- specific IPD and are presented as cases per 100,000 persons.
From 1998─2019, b efore introduction of conjugate vaccines in the US, incidence rates of IPD
among children <5 years of age were approximately cases per 100,000 persons. PCV13 -type
IPD caused the majority of disease. Note that 6C included with the PCV13 serotypes due to
cross- protection provided from the 6A antigen included in the vaccine. After the introduction of
PCV7 in 2000, rates of IPD declined significantly. There were additional declines in disease following PCV13 introduction in 2010. Around 2013, declines in PCV13-type IPD rates
plateaued at <2 cases per 100,000. This trend continued onward through 2019. Rates of overall
IPD are now <10 cases per 100,000 persons, with much of the remaining disease caused by
non-PCV13 serotypes.
Focusing on more recent years from 2007─ 2021 , the COVID -19 pandemic resulted in a 50%
reduction in rates of overall IPD in 2020 compared with 2018─2019. However, rates began to
rebound in 2021 with a 30% increase compared to 2020 rates. Data for 2022 are not yet
finalized, but looking at 2021 data by month, the monthly rates of IPD were back to the pre -
pandemic levels after around August 2021. IPD rates were examined for individual serotypes in
PCV13 among children <5 years of age from 2011 ─2021. After PCV13 introduction in children,
rates of IPD declined for many PCV13 serotypes. However, reductions were not seen in
serotype s 3 or 19F. Together, these serotypes accounted for almost 80% of remaining PCV13-
type disease in 2018 and 2019. The impact of the COVID -19 pandemic led to a change in the
serotype distribution of PCV13- type disease . In 2020 and 2021, serotype 19F rebounded
quickly and now accounts for the majority of remaining disease, while the proportion caused by
serotype 3 has declined. This will continue to be monitored to determine whether these changes
continue.
Now to review the current pediatric IPD burden among PCV15 and PCV20 serotypes , this table
shows the serotypes contained in the 3 conjugate vaccines and PPSV23. Serotypes covered by
PCV13 are shown in yellow ; additional serotypes covered by the new conjugate vaccines,
PCV15 and PCV20, are shown in green; and PCV15 contains the 13 serotypes included in
PCV13 plus serotypes 22F and 33F :
For analysis purposes: PCV13+6C: includes serotype 6C with PCV13 types due to cross protection from 6A antigen
PCV15 non- PCV13: includes serotypes 22F and 33F
PCV20 non- PCV15 : includes serotypes 8, 10A, 11A, 12F, and 15B
PPSV23 non -PCV20: includes serotypes 2, 9N, 17F, and 20
44

       Rates of IPD incidence among children <5 grouped by vaccine type from 2011─ 2021 remained
relatively stable for PCV15 /non-PCV13 and PCV20/ non-PCV15 serotypes in recent years
before the COVID -19 pandemic. Although rates of IPD were lower in 2020 and 2021, PCV15 /
non-PCV13 and PCV20/ non-PCV15 serotypes still account for a similar proportion of IPD at
around 15% each. There has been great variability over the years among children 5─18 years
of age, which is likely due to having much fewer number of cases. Unlike what was observed for
younger children, IPD did not start to rebound in 2021 among children 5─18 years of age.
Children with immunocompromising conditions are at increased risk of IPD. In terms of IPD
among children with select immunocompromising conditions, children <5 years of age with a
hematologic malignancy had rates of IPD around 230 times higher than children without a
hematologic malignancy. African -American children with sickle cell disease had rates of IPD at
around 30 to 70 times higher than African- American children without sickle cell disease,
depending upon their age. Among children with immunocompromising conditions, a higher
proportion of IPD is caused by non -vaccine serotypes compared to children without
immunocompromising conditions.
To review the impact of PCV13 on AOM and available data on incidence estimates for AOM,17
AOM is a major cause of childhood morbidity and pneumococcus is a common cause of AOM,
accounting for around a quarter of bacterial AOM. Studies have shown that AOM incidence has
decreased after PCV13 introduction, with declines ranging from 11% to 14% depending on the
age groups and years examined. AOM estimates vary among studies, but incidence is
consistently highest among children <5 years of age.
Regarding the data on the impact of PCV13 on all -cause and pneumococcal pneumonia and
estimated incidence of pneumonia in children , multiple studies have shown reductions in all -
cause and pneumococcal pneumonia among children following introduction of PCV13. Reductions in all -cause pneumonia range from 17% to 35% among children, depending on the
age group, with reductions largest among children <2 years of age . There was an estimated
40% reduction in pneumococcal pneumonia among children <1 year of age and a 51%
reduction in pneumonia among children 5─17 years of age . To summarize all -cause pneumonia
and all -cause inpatient pneumonia incidence estimates in cases per 100,000 person years
among children , pneumonia incidence is lower than AOM incidence but higher than IPD
incidence. Again, the highest incidence is observed among children <5 years of age.
In conclusion, the use of PCVs has significantly decreased the incidence of pneumococcal
disease in US children. However, risk of disease remains higher among children with
immunocompromising conditions compared to those without. In 2018 and 2019, the proportion
of IPD caused by vaccine serotypes was about 15% of IPD for PCV15 /non-PCV13 serotypes
and about 30% of IPD for PCV20 /non-PCV13 serotypes.
17 Tong et al. BMC 2018; King et al. ASHE 2021; Casey et al Clin Pediatr 2014; Kaur et al. EJCMID 2022
45

     Estimating the Impact of Higher -Valency PCVs on Pediatric Outpatient ARI Visits and
Antibiotic Use
Laura King, MPH (UC Berkeley) presented results from a University of California Berkeley
study estimating p ediatric outpatient ARI visits and antibiotic use attributable to serotypes in
higher valency PCVs. This presentation focused on pediatric outpatient visit and anti biotic
prescription incidence, AOM vaccine serotype attributable proportion and incidence, and
sinusitis and pneumonia vaccine serotype attributable proportion and incidence. In terms of
background, ARIs account for a large proportion of all outpatient visits and antibiotic
prescriptions among children. Previous work looking at a commercially -insured population
established that there were over 1,200 ARI visits per 1,000 children in 2018.18 A separate study
established that there were about 250 ARI -associated antibiotic prescriptions per 1,000 children
issued from US doctors ’ offices and EDs per year in 2014 and 2015.19 Streptococcus
pneumoniae (S. pneumoniae) is a known etiology of several ARIs, including AOM , sinusitis, and
pneumonia. However, the contribution of pneumococcus to the total burden of these conditions
and the visits and antibiotic prescriptions associated with them is still unknown.
Time series data demonstrate decreases in outpatient visits and antibiotic use associated with
PCVs. A previously published study examining the number of all antibiotic prescriptions per
1,000 persons stratified by age group20 showed that the rate of antibiotic prescriptions
decreased from 2011 to 2014, coinciding with uptake of PCV13 after its introduction in 2010.
This decrease was especially pronounced in children <2 years of age, the age group eligible for
vaccination. In considering PCV20 and PCV15 for pediatric use, it is important to better
understand the potential impacts of these higher valency vaccines on outpatient visits and
antibiotic use. This was the impetus for the current study with an overall objective to estimate
the incidence of pediatric outpatient visits and antibiotic prescriptions for AOM , sinusitis, and
pneumonia caused by S. pneumoniae serotypes found in the new higher valency PCVs, PCV15
and PCV20. This study focuses on the additional serotypes in PCV15 and PCV20 that are not in
PCV13 to quantify the additive potential of these vaccines. These are referred to as PCV20 -13
and PCV15- 13 serotypes.
The study focuses specifically on AOM , abbreviated AOM, sinusitis, and pneumonia as these
are ARIs with established pneumococcal involvement. The overall study objective is composed
of two parts , which are to: 1) estimate the incidence of all- cause visits and antibiotic
prescriptions for these conditions; and 2) estimate the proportion of outpatient disease caused
by PCV15 -13 and PCV20- 13 serotypes. Multiplying the results from these 2 components will
provide the incidence of visits and antibiotic prescriptions for these conditions attributable to
PCV15 -13 and PCV20- 13 serotypes.
Beginning with the first project component to estimate all-cause vi sit and antibiotic prescription
incidence for AOM, pneumonia, and sinusitis , 2 data sources were used to capture visits and
antibiotic prescriptions across all outpatient settings in the US. Visits to and antibiotic
prescriptions from physician offices and EDs were estimated using the National Ambulatory
Medical Care Survey (NAMCS ) and the National Hospital Ambulatory Medical Care Survey
(NHAMCS ). These are nationally representative surveys administered by CDC ’s National
Center for Healthcare Statistics (NCHS) . Data were used from 2016 and 2018, as later years
and in 2017 were not available in NAMCS at the time of the analysis. Because NAMCS and
18 King LM, et al. Antimicrob Steward Healthc Epidemiol. 2021;1(1):1- 8. doi: 10.1017/ash.2021.230
19 Hersh AL, et al. Clin Infect Dis. 2021;72(1):133- 137. doi: 10.1093/cid/ciaa667
20 King et al., Clin Infect Dis. 2020; 70(3):370- 377). doi: 10.1093/cid/ciz225
46

  NHAMCS only cover physician offices and EDs, the MarketScan Commercial and Medicaid
Databases were used to estimate visits and prescribing in alternative outpatient settings such as
urgent care and retail health clinics. In both datasets, a single diagnosis was assigned to each
visit using an established tiered methodology that prioritizes diagnoses most likely to result in an
antibiotic prescription. All incidence estimates were standardized per 1,000 person -years at risk
and total incidence was estimated by combining the sum of the estimates from NA MCS ,
NHAMCS , and Market Scan. Using those methods, total incidence of outpatient visits for all 3
conditions was estimated to be 208 visits per 1,000 person -years . Total incidence of outpatient
antibiotic prescriptions was estimated to be 181 prescriptions per 1,000 person- years . Notably ,
overall incidence was driven primarily by AOM .
In terms of the second project component and estimating vaccine serotype attributable
proportions and incidence, it is important to note that there are several major challenges in
evaluating pneumococcal and serotype -specific contributions to outpatient disease. First,
children are frequently colonized with pneumococcus . Published estimates of nasopharyngeal
pneumococcal carriage range from 11% to 60% in healthy children from h igh-income countries.
Second, samples from infection sites are not regularly obtained for outpatient pneumococcal disease. There are some studies using samples of middle ear fluid in children with AOM.
However, the children sampled in these studies often have severe or recurrent disease. Third,
few studies have been conducted for non- AOM ARIs in pediatric outpatients.
Given these challenges, 3 methods were used to estimate the proportion of outpatient AOM
attributable to PCV15- 13 and PCV20- 13 seroty pes. All of these methods have their own
limitations, and no one method is likely definitive. However, using multiple methods allowed for
estimation of ranges of likely values, taking into account the uncertainties inherent in estimating
etiology in outpatient disease. For all methods, previously published data were used to generate
estimates. The first method used was a vaccine probe approach. In vaccine probe studies, VE
against vaccine type in all -cause disease is used to estimate the proportion of disease
attributable to a specific pathogen, in this case, the vaccine serotypes. The second approach
used considered pneumococcal prevalence and serotype distribution for middle ear fluid
sampled from children with AOM to estimate attributable proportions. The third approach used
differen tial nasopharyngeal carriage prevalence in children with AOM and healthy children to
estimate the pneumococcal attributable proportion and combined this with the distribution of
serotypes and carriage in children with AOM.
Using these 3 methods, pneumococcus was estimated to account for 14 % to 22% of outpatient
AOM cases , PCV15 -13 serotypes account ed for 0.7 % to 1% of outpatient AOM, and PCV20- 13
serotypes account ed for 3.7 % to 5.1% of outpatient AOM. The highest attributable percents
were observed from the approach using pneumococcal prevalence and serotype distribution in
middle ear fluid. Regardless of method, the distribution of vaccine serotype groups remained
fairly constant, with PCV20- 13 serotypes accounting for about 5 times the proportion of
outpatient disease covered by PCV15- 13 serotypes. Using these attributable percents and the
all-cause AOM visit and prescription incidence data presented earlier, incidence was estimated
for outpatient visits per 1,000 person- years and the annual number of outpatient AOM visits in
children. It was estimated that 76 ,000 to 109,000 visits per year were attributable to PCV15- 13
serotypes and 397,000 to 543,000 visits were attributable to PCV20- 13 serotypes. Looking at
the same data for AOM -associated antibiotic prescriptions , PCV15 -13 serotypes were
associated with 65,000 to 93,000 outpatient antibiotic prescriptions annually and PCV20- 13
serotypes were associated with 340 ,000 to 464,000 outpatient antibiotic prescriptions annually.
47

  Regarding the attributable proportion and incidence estimates for pneumonia and sinusitis , less
data were available for these conditions. The ability to estimat e attributable proportions in
pneumonia and sinusitis was limited to the vaccine probe and differential carriage approaches.
Using these methods, 12 % to 18% of pediatric outpatient pneumonia were estimated to be
attributable to pneumococcus . PCV15 -13 serotypes account ed for less than 1% of outpatient
pediatric pneumonia cases and PCV20- 13 serotypes accounted for 2.8 % to 4.4% of outpatient
pediatric pneumonia cases. The attributable proportions were multiplied by the all -cause visit
and antibiotic prescription estimates presented earlier , which estimate d that PCV15 -13
serotypes account ed for 9,000 to 14,000 visits and 7,000 to 11,000 antibiotic prescriptions for
outpatient pediatric pneumonia per year . PCV20 -13 serotypes account for 43,000 to 68,000
visits and 34 ,000 to 53,000 antibiotic prescriptions for outpatient pediatric pneumonia per year.
For sinusitis, it was estimated that 12% to 30% of all outpatient pediatric cases were attributable
to pneumococcus . PCV15 -13 serotypes account ed for 0.6 % to 1.5% of sinusitis cases and
PCV20 -13 serotypes account ed for 2.8 % to 7.3% of sinusitis cases. The differential carriage
estimates were the same for pneumonia and sinusitis because the same estimates were used
for all non- AOM ARIs in that approach given the scarcity of data. For sinusitis, it was estimated
that PCV15- 13 serotypes account ed for 17,000 to 44,000 visits and 16 ,000 to 43,000 antibiotic
prescriptions per year . PCV20 -13 serotypes account ed for 82,000 to 216,000 visits and 79 ,000
to 209,000 antibiotic prescriptions per year.
To summarize the ranges of point estimates for each condition by vaccine serotype group
estimated using the multiple methods described earlier, for all 3 conditions, PCV15- 13
serotypes account ed for 1.9 % to 3.4% of outpatient disease in children, translating to 103,000 to
168,000 pediatric outpatient visits and 90,000 to 148,000 outpatient antibiotic prescriptions
annually in the US. PCV20- 13 serotypes account for 9.4% to 16.8% of outpatient AOM,
pneumonia, and sinusitis, translating to 527,000 to 831,000 pediatric outpatient visits and
458,000 to 731,000 outpatient antibiotic prescriptions annually in the US.
This study had several limitations. First, it relied upon previously published data to estimate
attributable proportions. Consequently, although data on pneumococcus in all outpatient
conditions was limited, this was especially true for sinusitis and pneumonia. Therefore, it was
necessary to rely on AOM as a proxy for these conditions in some cases. Additionally, due to
data limitations at the time of the analysis, the incidence estimates were based on all- cause
incidence data from 2016─ 2018. Finally, it was assumed that healthcare utilization was constant
across serotypes for outpatient disease.
In conclusion, this study estimated that the additional serotypes included in PCV15 and PCV20
accounted for approximately 100,000 to 830,000 outpatient visits and 90,000 to 730,000
outpatient antibiotic prescriptions for AOM, pneumonia, and sinusitis in US children annually.
Specifically, PCV15 -13 serotypes account ed for 103,000 to 168,000 visits and 90,000 to
148,000 antibiotic prescriptions . PCV20 -13 serotypes account for 527,000 to 831,000 visits and
458,000 to 731,000 antibiotic prescriptions. The percent of outpatient disease attributable to
PCV2 0-13 serotypes was greater than the percent attributable to PCV15- 13 serotypes. As a
result, the estimated incidence of outpatient pediatric visits and antibiotic prescriptions
attributable to PCV20- 13 serotypes was 4 to 5 times that attributable to PCV15 -13 serotypes.
48

      PCV20 Phase 2/3 Study Results among Children
Wendy Watson, MD (Pfizer) presented key results from Pfizer’s PCV20 Pediatric Clinical
Development Program from the Phase 2/3 trial. PCV20 is built on the 20- plus year legacy of
PCV7 and PCV13 . PCV20 contains all of the components of PCV13, with 7 additional
conjugates. Pfizer is seeking to expand PCV20 currently licensed in adults to include the same
pediatric indications as PCV13. PCV20 builds upon the clinical experience of previous
generations of PCV7 and PCV13 . PCV7 was licensed based on a randomized controlled clinical
(RCT) efficacy trial of IPD in California. In this study of 38,000 infants, high efficacy was
demonstrated. Subsequently, high VE was shown following PCV7 introducti on. When PCV13
was developed to expand protection against 6 additional serotypes, it was not considered
feasible to perform an efficacy trial. Therefore, a licensing pathway similar to other vaccines, like
a conjugate vaccine, was pursued. Immunogenicity bridging comparing PCV13 to PCV7 was
used to support licensure globally. Similarly, PCV20 licensure for pediatrics will be based on
immunogenicity bridging with non- inferiority comparisons to PCV13—a vaccine that now has
more than 10 years of demonstrated effectiveness against disease due to vaccine serotypes.
This table shows the studies Pfizer submitted to the FDA to support the PCV20 pediatric
indication:
These pediatric studies were generally modeled on the PCV13 pediatric studies and consist ing
of Phase 2 and Phase 3 studies. The studies listed in the table were conducted in children in the
US, including Puerto Rico, except for the safety study on the bottom row that also included
infants from other countries. For this presentation, Dr. Watson focus ed on the pivotal
immunogenicity study in infants in the second row and the single dose study in children in the
third row.
The Phase 3 pivotal infant trial was a multi- center , randomized , double- blind study enrolling
infants in the US, including Puerto Rico. The study enrolled approximately 2,000 participants
who were randomized equally to receive 4 doses of PCV20 or PCV13. PEDIARIX and HIBERIX
were given concomitantly with the first 3 doses and MMR and varicella vaccines were given with
the fourt h dose. Influenza and rotavirus vaccines were permitted to be given with study vaccine
in age-eligible participants. Blood was collected for immunogenicity assessments 1 month after
the third dose, before the fourth dose, and 1 month after the fourth dose. The primary study
objectives were to : 1) describe safety ; 2) evaluate the immunogenicity of PCV20, including non-
inferiority comparisons of PCV20 to PCV13; and 3) assess responses of specific concomitantly
49

         administered vaccines. In terms of the dispositio n and demographics of the study population,
the groups were well -balanced with respect to sex, race, and ethnicity.
PCV generate complex and diverse cellular and humoral immune responses that play a role in
imparting protection. The primary and key secondary objectives that were agreed to
prospectively with the FDA include 2 co- primary objectives to assess noninferiority of
immunoglobulin G (IgG) geometric mean concentrations ( GMCs ) after the toddler dose and
assess n oninferiority of the percentage of participants with IgG above predefined levels after the
infant series. The key secondary objective was to assess noninferiority of IgG GMC after the
infant series . Other aspects of the responses also were assessed, including other IgG
respons es, functional antibodies measured as opsonophagocytic activity (OPA) titers, and
boosting of IgG and OPA antibody levels that are indicative of immune memory. The
assessment of the totality of data for serotypes that missed non -inferiority was agreed to
prospectively by the FDA. An example of how important this assessment is comes from the
previous experience with PCV13 and serotypes 6b and 9b. These 2 serotypes missed a co-
primary objective for non -inferiority compared to PCV7, but the totality of immunogenicity data
supported licensure and subsequent real -world effectiveness has shown that PCV13 protects
against IPD caused by these two serotypes.
For the co -primary objective percentage of participants with the predefined IgG concentration
after dose 3, non-inferiority was declared if the 95% confidence interval of the difference was
greater than - 10%. The additional 7 serotypes were compared to the lowest result in the PCV13
group, excluding serotype 3. In this case, the comparison was to serotype 23F result in the
PCV13 group. For this objective, non -inferiority was met for 14 serotypes and 6 serotypes
missed non-inferiority, although serotypes 1, 4, 9V, and 23F missed statistical non- inferiority by
only a small margin. Serotypes 3 and 12F missed by a gr eater margin, but the totality of data
was supportive. Additionally, public reference standard that was used to calculate 12F IgG
concentrations may be underestimating 12f IgG results . Pfizer has shared these findings with
the FDA.
Continuing to look at t he response after Dose 3, the IgG GMC ratios in the PCV20 group
compared to the PCV13 group for each vaccine serotype was the key secondary objective in
the study. Non-inferiority was to be declared for this objective if the lower bound of the 95%
confidence interval of the ratio was greater than 0.5. All 20 serotypes met non- inferiority for this
comparison, including serotypes 3 and 12F. There also was comparison of the 7 additional
serotypes to the result of a vaccine serotype in the PCV13 group. The IgG GMCs to those 7
additional serotypes in the PCV13 group after Dose 3 were low. The IgG GMC s for the 7
additional serotypes were substantially higher in the PCV20 group compared to the PCV13
control group. This was also the case after Dose 4. Functional antibodies elicited by the vaccine
after Dose 3 also were assessed. The OPA GMC responses for the 13 matched serotypes were
similar between groups, even for serotypes that missed the co -primary IgG objective for this
dose. PCV20 also elicited very robust functional activity to the 7 additional serotypes, including
12F.
Moving on to the response after the toddler dose, Dose 4 in the study , non-inferiority was
declared if the lower confidence interval was above 0.5. Similar to the result for the IgG GMC
ratios after Dose 3, all 20 vaccine serotypes met non- inferiority after Dose 4. An important
property of conjugate vaccines is their ability to elicit memory responses. Looking at the
antibody levels in the PCV20 group after Dose 3 and after Dose 4 , it is clear that there were
numerically higher antibody levels after the toddler dose than after the infant series. This was
observed for both IgG GMCs and OPA GMTs for the vaccine serotypes. This indicates that
50

  immune response after the toddler dose is a significant marker indicating that a memory
response has been induced after the infant series by PCV20.
In addition to evaluating the pneumococcal responses, Pfizer evaluated responses to
concomitant vaccines. Regarding the difference in percent of part icipants with pre- specified
antibody levels to the different antigens in PEDIARIX and HIBERIX given with the 3 infant doses
of PCV20 or PCV13 , all met the non- inferiority criteria. In terms of the responses to MMR and
varicella vaccines given with D ose 4 of PCV20 or PCV13 , all met the non- inferiority criteria.
These data support PCV20 use in routine pediatric schedules.
Regarding safety , injection site pain, drowsiness, and irritability were the most common events.
Most reactions were mild or moderate , rates were similar across both groups , and were
consistent with the historical experience with PCV13. As mentioned previously, another
important Phase 3 study assessed the safety and immunogenicity of a single dose of PCV20 in
children 15 months to less than 18 years of age. This study was conducted in the US to support
the use of PCV20 in children through 17 years of age. This multi- center,  single arm trial enrolled
approximately 800 healthy participants of approximately 200 per age group. Partic ipants 15
months ─5 years of age were required to have documentation of at least 3 doses of PCV13 prior
to enrollment. In terms of IgG GMCs for the 2 age groups less than 5 years of age, 1 dose of
PCV20 elicited a robust IgG response to all 20 serotypes in children 15 to <24 m onths and 2 to
<5 Years previously vaccinated with PCV13. Data from the youngest group also supports the
potential for replacement of PCV13 with PCV20 in the schedule. There was a similar pattern in
the functional antibody responses in these age groups , as well as IgG and OPA responses in
older children. The safety data were consistent with historical experience with PCV13. There
were no clinically significant differences in the AEs in the PCV20 and PCV13 control group.
SAEs were reported in 4.5% of PCV20 recipients and 3.7% of PCV13 recipients in the infant
studies supporting US licensure. No SAEs in this dataset were considered to be related to
vaccine and no deaths were reported.
In summary, PCV20 is well- tolerated when administered as a 4-dose series to infants and as a
single dose to toddlers through older children, with a safety profile similar to PCV13. The totality
of data shows that PCV20 elicits IgA, IgG, and OPA responses in infants for all vaccine
serotypes consistent with PCV13. A single dose of PCV20 elicited IgG and functional immune
responses to all 20 serotypes in children 15 months to less than 18 years of age, including
those with prior PCV13. PCV20 is compatible with routine pediatric vaccines. PCV20 is currently
under review by the FDA for use in pediatric populations 6 weeks to less than 18 years of age,
with a target action date in April 2023. PCV20 has the potential to address the substantial
burden of pneumococcal disease in children.
Preliminary EtR /GRADE for PCV20 use in US Children
Miwako Kobayashi, MD, MPH (CDC/NCIRD) provided the EtR Framework for PCV20 use in
US children, pointing out that while the EtR includes 7 domains, the focus of this session would cover 3 of the domains: P ublic Health Problem, Benefits and Harms, and Equity. Currently , all
children under 2 years of age have the same pneumococcal vaccine recommendations to
receive either PCV13 and PCV15 using a 3- dose series at 2, 4, and 6 months of age and a
booster dose at 12 to 15 months of age. Children ≥2 years of age with certain underlying
conditions are recommended to receive PPSV23 in addition.
51

       For this EtR analysis, there were 2 policy questions:
Should PCV20 be recommended as an option for pneumococcal conjugate vaccination
according to currently recommended dosing and schedules for US children aged <2 years?
Should PCV20 without PPSV23 be recommended as an option for pneumococcal vaccination for US children aged 2– 18 years with underlying medical conditions that
increase the risk of pneumococcal disease?
Combined into the PICO question regarding whether PCV20 should be recommended as an
option for pneumococcal vaccination for US children, the population is all US children aged <2
years and US children aged 2–18 years with underlying medical conditions. The comparison is
the current recommendations for the respective groups. The critical outcomes include: Vaccine-Type IPD ( VT-IPD), VT-Pneumonia, VT -AOM, VT -Pneumococcal Deaths, and SAEs F ollowing
Vaccination.
Beginning with the Public Health domain, use of pneumococcal conjugate vaccines significantly
decreased the incidence of pneumococcal disease in US children. Outpatient acute respiratory
illness caused by pneumococcus such as AOM , sinusitis, and pneumonia are common causes
of outpatient visits and antibiotic prescribing. The risk of disease remains high in children with
underlying conditions that increase the risk of pneumococcal disease. In 2018─2019, the
proportion of IPD caused by vaccine serotypes was approximately 30% for additional serotypes
contained in PCV20 but not in PCV13 and 15% for additional serotypes contained in PCV15
and not in PCV13.
21 The WG determined that pneumococcal disease is of public health
importance for both groups of children. There was variability in the WG’s interpretation for
children <2 years of age due to the significant reductions in pneumococcal disease among
these children. However, most WG members agreed that pneumococcal disease continues to
be of public health importance due to the remaining disease burden.
For the B enefits and Harms domain, the WG interpretation of this domain was informed
primarily by the great evidence profile for the PICO question. The outcomes deemed critical
were VT-IPD, VT-pneumonia, VT-AOM, and VT-pneumococcal deaths. Given that there are
currently no studies assessing PCV20 effectiveness against these clinical outcomes , PCV20
immunogenicity studies were used as evidence for these outcomes. To supplement this, the
WG also reviewed post -licensure PCV13 and PPSV23 effectiveness data against these
outcomes as a background.
Regarding outcomes related to harms, WG members deemed SAEs as being of critical
importance. Evidence of SAEs was available and reviewed for PCV20. First, a summary of the
post-licensure PCV13 VE data. Several post -licensure studies assessed PCV13 effectiveness
against IPD. In general, these studies showed that PCV13 is highly effective against VT-IPD.
Data on PCV13 effectiveness against VT-pneumonia in children are limited. Based on the 2
studies done in China and Israel, PCV13 is likely to be protective against VT-pneumococcal
pneumonia, but with a wide confidence interval. Data on PCV13 effectiveness against VT-
pneumococcal AOA also are limited. Estimates from these studies also tend to have wide
confidence intervals, though the data suggest that PCV13 is likely protective against VE-
pneumococcal AOM .
21 Gierke. February 2023 ACIP meeting presentation; King. February 2023 ACIP meeting presentation
52

 Data on PPSV23 effectiveness against pneumococcal disease in children with underlying
conditions are limited.22 A study conducted before the introduction of PCV in the US showed
that PPSV23 is protective against VT-IPD among children with underlying medical conditions.23
Data on PPSV23 effectiveness against non- invasive pneumococcal disease in children are even
more limited. In a recent systematic review, no studies were identified that assessed PPSV23
VE against AOM . Two RCTs that evaluated the efficacy of administrating both PCV7 and
PPSV23 against AOM did not show any efficacy in the intervention groups.24
To summarize the data on PCV20 use in children, the WG conducted a systematic review of
literature on PCV20 use among children.25 Overall, 4 studies were included for GRADE
(Grading of Recommendation Assessment, Development and Evaluation) . Of these, 3 were
considered for evidence of routine PCV20 use and 1 was considered for evidence of PCV20
use in children with underlying medical conditions. Evidence of benefits of PCV20 use among
children <2 years of age was informed by 2 RCTs (Phase II and III) that randomized healthy
children to receive either PCV13 or PCV20.26 In the pivotal trial , PCVs were given using the 3-
dose primary series followed by a booster dose. The study showed that PCV20 had numerically
lower immune responses compared with PCV13 for most of the 13 shared serotypes. Post -dose
3, PCV20 did not meet the non- inferiority criteria compared with PCV13 for some serotypes for
the primary immunogenicity outcome. Post -dose 4, PCV20 met the non- inferiority criteria
compared with PCV13 for all 13 shared serotypes and for all 7 additional serotypes. Evidence of
harms was informed by findings from 3 RCTs .27 Across the 3 studies, SAEs were reported in
4.5% of the PCV20 recipients compared with 3.7% of the PCV13 recipients, but none were
considered to be vaccine -related.
The overall certainty of evidence was moderate. Certainty of evidence for benefits was
downgraded since these are immunogenicity studies and there are no correlates of protection
established for most outcomes of interest. For harms, certainty of evidence was downgraded for
imprecision due to lack of vaccine- related SAEs being reported. The WG determined that the
desirable anticipated effects of PCV20 were moderate. PCV20 provides the broadest serotype
coverage among available PCVs, so it is expected to prevent more disease. However, it is
unknown how substantial the protection conferred from PCV20 will be based on available data.
The undesirable anticipated effects were considered to be minimal. The WG’s interpretation of
whether the desirable effects outweigh the undesirable effects was split between “favors
intervention ” of PCV20 use and “favors both ” the intervention and the compar ator of either
PCV13 or PCV15 use. Those who favor ed the intervention believe that PCV20 is expected to
prevent more disease compared with current PCVs. Those who favor ed both consider ed the
uncertainties of the clinical implications of the lower immunogenicity of PCV20 and improved
immunogenicity of PCV15 against serotype 3 compared with PCV13.
22 Marra et al. Value Health 2022
23 Fiore et al. EID 1999
24 Veenhoven et al. Lancet 2003; and Van Kempen et al. Int J Pediatr Otorhinolaryngol 2006
25 The search strategy and search terms used are available in the supplementary slides from this presentation
26 Senders et al. PIDJ 2021; and Pfizer unpublished data from B7471011
27 Senders et al. PIDJ 2021; Pfizer B7471011, unpublished data; Pfizer B7471013, unpublished data, limited to US and Puerto Rico
sites
53

         Findings from the pediatric PCV15 immunogenicity studies were presented during the February
2022 ACIP meeting.28 No studies were conducted among children 2─ 18 years of age with
underlying medical conditions . Evidence on benefits was informed by 1 Phase 3 non -
randomized clinical trial with no comparator that evaluated the safety and immunogenicity of
PCV20 use in healthy children 15 m onths ─17 years of age. This included children <5 years of
age who received at least 3 doses of PCV13. All participants received a dose of PCV20. The
study showed that PCV20 was immunogenic for all 20 vaccine serotypes when assessed 1
month after vaccination compared with pre- vaccination baseline. SAEs after vaccination was
reported in 0.6% of the participants and none were considered to be vaccine- related.
The overall certainty of evidence was very low. Certainty of evidence was downgraded furthe r
for this study since this was an open -label non- randomized controlled trial with no comparator
group and did not include children with underlying conditions. The WG determined that the
desirable anticipated effects of PCV20 use were moderate, the reasons for which were similar
to those for routine use for children <2 years of age. In addition, there are no data on PCV20
use among children with underlying medical conditions. The undesirable anticipated effects
were considered to be minimal. The WG’s interpretation of whether the desirable effects
outweigh the undesirable effects was split between “ favors intervention” of PCV20 use and
“favors both ” the intervention and the comparator of PPSV23 use after currently recommended
PCV doses. Those who favored the intervention believed that PCV20 is expected to prevent
more disease compared with current recommendations. Those who favored both consider ed the
fact that there are no data on PCV20 use in this population and that the clinical implications of
improved immunogenicity of PCV15 against serotype 3 compared with PCV13 are unknown.
For the E quity domain, data were reviewed of estimated pneumococcal conjugate vaccine
coverage by 24 months of age among children born during 2018─ 2019 by health insurance
status using data from the National Immunization Survey -Child (NIS-Child) . Compared with
coverage among children with private insurance only, children who were uninsured and those
insured by Medicaid and other insurance was lower. Nationally representative PPSV23 vaccine
coverage data among children with indications are limited. In a study among children enrolled in the Michigan Medicaid program,
29 64% of children with sickle cell anemia received 4 doses of
PCV followed by a dose of PPSV23 as recommended by 5 years of age and 53% received 4
doses of PCV followed by 2 doses of PPSV23 as recommended by 10 years of age . Other
studies that assessed PPSV23 coverage among children with underlying medical conditions
were much lower, ranging from 20% t o 40%.30
An unpublished analysis using CDC ’s ABCs data assessed the incidence rate difference of IPD
among children ≤17 years of age in the highest and the lowest Census tract poverty categories
by year for all serotypes, PCV13 serotypes, PCV15/ non-PCV13 serotypes, PCV20/n on-PCV13
serotypes, PCV20 /non-PCV15 serotypes, and non- vaccine serotypes from 2010─ 2019. For all
serotypes in PCV13 serotypes, incidence rate difference decreased after 2010 after PCV13 was recommended for use in children. There was essentially no incidence rate difference for
PCV15 /non-PCV13 serotypes in 2018─ 2019. The IPD incidence rate difference for the
additional serotypes contained in PCV20 remained, and there was a slightly larger incidence
rate difference for non -vaccine serotypes.
28 Banniettis.
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Summary: MEETING OF THE ADVISORY  COMMITTEE ON IMMUNIZATION  PRACTICES (ACIP)  FEBRUARY 22 -24, 2023  MEETING SUMMARY  CONTENTS   WEDNESDAY: FEBRUARY 22, 2023 .......................................................................................................... 5  WELCOME AND INTRODUCTIONS ...................................................................................... 5  Call to Order/Roll Call…