07 RSV Adults Melgar 508

Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.
RSV Vaccination in Older Adults:
Benefit -Risk Discussion
Michael Melgar , MD
Lauren Roper, MPH
Advisory Committee on Immunization Practices
February 29, 2024
There are two RSV vaccines approved in the United States
and recommended for adults aged ≥60 years, using shared
clinical decision -making.
Slide credit: https://stacks.cdc.gov/view/cdc/108883
Estimated benefits
of RSV vaccination
(single dose) with
GSK’s Arexvy  and
Pfizer’s Abrysvo ,
stratified by agePotential risk  of
Guillain -Barre
syndrome (GBS) after
RSV vaccination with
GSK’s Arexvy  and
Pfizer’s Abrysvo
2
▪Estimated benefits
–Estimated numbers of preventable RSV illnesses over  two
consecutive seasons , per 1 million vaccine doses administered to
adults 60 years and older1
•Outpatient visits, hospitalizations, intensive care unit (ICU)
admissions, in -hospital deaths
–Informed by published incidence rates, RSV surveillance data
from CDC, and estimated vaccine efficacy from clinical trials
▪Potential risk
–Informed by rate of GBS per 1 million vaccine doses
administered to adults 60 years and older1 observed in FDA
analysis of data from the FDA -CMS partnership2
–Preliminary data did not permit estimation of attributable (i.e.,
excess) risk, so observed rates are also compared with rates
expected from backgroundOverview of comparisons
1. This analysis assumes 100% uptake of RSV vaccine, with a single dose, in a cohort of 1 million older adults.
2. Analysis of administrative claims data using a 42 -day risk interval, adjusted for delays in claims data. https://bestinitiative.org/wp -content/uploads/2024/01/BEST_RSV_Safety_Older_Adults_2023 -2024.pdf
3
Estimated age distribution of national RSV -associated hospitalizations, ICU admissions, and in -
hospital deaths among adults ≥18 years, RSV -NET, 2022 –2023, compared with U.S. population
Unpublished data. Underlying rates are adjusted using multipliers for the frequency of RSV testing during each season and for  the sensitivity of RSV diagnostic tests. Estimates
from 2022 -2023 are preliminary. These estimates use the same multipliers as for 2019 -2020.
*As of 2022. https://www.census.gov/popclock/  42.9%
37.1%
58.0%
9.2%23.9%
26.8%
22.8%
13.0%20.4%
22.6%
11.3%
24.1%12.8%
13.6%
7.9%
53.7%
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%Hospitalizations
ICU admissions
In-hospital deaths
U.S. Adult Population*≥75 65-74 50-64 18-49
U.S. Adult Population *Age group, years:
4
0100200300400500600
2016-17 2017-18 2018-19 2019-20 2020-21 2021-22** 2022-23**Annual RSV -associated hospitalizations
per 100,000 population 18-49 50-54 55-59 60-64 65-69 70-74 75-79 ≥80
Unpublished data. Rates are adjusted using multipliers for the frequency of RSV testing during each season and the sensitivit y of RSV diagnostic tests.
*Estimated rates exclude recorded hospitalizations among pregnant adults.
**Estimates from 2021 -2022 and 2022 -2023 are preliminary. These estimates use the same multipliers as for 2019 -2020.
https://www.cdc.gov/rsv/research/rsv -net/index.html  Estimated annual RSV -associated hospitalization  rates per 100,000 adults*
aged ≥18 years by age group and year, RSV -NET, 2016 –17 to 2022 –23
Age group, years:
5
0100200300400500600
2016-17 2017-18 2018-19 2019-20 2020-21 2021-22** 2022-23**Annual RSV -associated hospitalizations
per 100,000 population 60-64 65-69 70-74 75-79 ≥80 Inputs : Estimated annual RSV -associated hospitalization  rates per 100,000
adults* aged ≥60 years by age group and year, RSV -NET, 2016 –17 to 2022 –23
Unpublished data. Rates are adjusted using multipliers for the frequency of RSV testing during each season and the sensitivit y of RSV diagnostic tests.
*Estimated rates exclude recorded hospitalizations among pregnant adults.
**Estimates from 2021 -2022 and 2022 -2023 are preliminary. These estimates use the same multipliers as for 2019 -2020.
https://www.cdc.gov/rsv/research/rsv -net/index.html  Age group, years:
6
▪Over the same surveillance seasons
(2016 -17 to 2019 -20, and 2022 -23):
–Calculated the proportions of hospitalized
adults in each age group who
•Were admitted to ICU
•Experienced in -hospital death
–Applied these proportions to the estimated
hospitalization rates*
–Estimated population -based rates of ICU
admission and in -hospital deathInputs : Estimated annual rates of RSV -associated ICU admission and
in-hospital death per 100,000 adults aged ≥60 years (RSV -NET)
*Unpublished data. Rates are adjusted using multipliers for the frequency of RSV testing during each season and the sensitivi ty of RSV diagnostic tests.
Estimated rates exclude recorded hospitalizations among pregnant adults.
Estimates from 2022 -2023 are preliminary. These estimates use the same multipliers as for 2019 -2020.
https://www.cdc.gov/rsv/research/rsv -net/index.html
7
05001,0001,5002,0002,500
18-49 50-64 ≥65 Annual RSV -associated outpatient visits
per 100,000 population
Age (years)Inputs : Estimated annual rates of RSV -associated outpatient visits  per 100,000
adults aged ≥18 years , meta -analysis of active surveillance studies, United States
Industry -sponsored (Pfizer): McLaughlin JM, Khan F, Begier  E, et al. Rates of Medically Attended RSV Among US Adults: A Systematic Review and Meta -
analysis. Open forum infectious diseases 2022 Jul; 9(7):ofac300. https://doi.org/10.1093/ofid/ofac300
8
Inputs : Summary of annual rates of RSV -associated illness
1. Industry -sponsored (Pfizer): McLaughlin JM, Khan F, Begier  E, et al. Rates of Medically Attended RSV Among US Adults: A Systematic Review and Meta -analysis. Open
forum infectious diseases 2022 Jul; 9(7):ofac300. https://doi.org/10.1093/ofid/ofac300
2. CDC RSV -NET data from surveillance seasons: 2016 -17 to 2019 -20 and 2022 -23. Values are based upon the average burden -adjusted ra tes and 95% confidence intervals
over those five seasons. Unpublished data.  https://www.cdc.gov/rsv/research/rsv -net/index.html
3. Kujawski SA, Whitaker M, Ritchey MD, et al. Rates of respiratory syncytial virus (RSV) -associated hospitalization among adults w ith congestive heart failure -United States,
2015 -2017. PLoS  One. 2022 Mar 9;17(3):e0264890. https://doi.org/10.1371/journal.pone.0264890
4. Industry -sponsored (Pfizer): Onwuchekwa C, Moreo LM, Menon S, et al.  Underascertainment  of Respiratory Syncytial Virus Infection in Adults Due to Diagnostic Testing
Limitations: A Systematic Literature Review and Meta -analysis. The Journal of Infectious Diseases. 2023 July; 228(2): 173 –184. https://doi.org/10.1093/infdis/jiad012  Outcome Values
Outpatient visits Published incidence rates and 95% confidence intervals.1
Hospitalizations RSV -NET2; age -dependent rates and 95% confidence intervals are based on laboratory -
confirmed RSV infections among hospitalized adults detected through clinician -driven testing,
and are adjusted for the frequency of RSV testing among adults hospitalized with respiratory
illness and for the sensitivity of diagnostic tests (burden adjustment).3 Assumed test sensitivity
incorporates recent literature showing increased diagnostic yield from multiple specimen
types, relative to nucleic acid testing of nasopharyngeal swab alone.4 Input values are taken as
the mean burden -adjusted rates over five RSV seasons (2016 -17 to 2019 -20, and 2022 -23).
ICU admissions Mean age -dependent rates and 95% confidence intervals of RSV -associated ICU admission
from RSV -NET over five seasons2
Deaths
(in-hospital only)Mean age -dependent rates and 95% confidence intervals of RSV -associated in -hospital deaths
from RSV -NET over five seasons2
9
Outcome (RSV -Associated) Arexvy , GSK1
VE (95% CI)Abrysvo , Pfizer2
VE (95% CI)
Season 1
(months 0 -7
post -injection)Season 2
(months 13 -18
post -injection )3Season 1
(months 0 -7
post -injection)Season 2
(months 8 -14
post -injection )3
Outpatient visits4
Trial efficacy against medically -attended
RSV ARI79.0%
(54.3, 91.5)27.8%
(0, 60.4)65.2%
(36.0, 82.0)55.0%
(0, 82.0)
Hospitalizations, ICU Admissions,
and In -hospital Deaths
Trial efficacy against medically -attended
RSV LRTD/LRTI87.5%
(58.9, 97.6)552.9%
(0, 81.2)584.6%
(32.0, 98.3)675.0%
(0, 97.4)6Inputs : Vaccine Efficacy (VE)
Point estimates were used in this analysis. Uncertainty in vaccine efficacy was not incorporated into uncertainty in estimate d preventable outcomes.
Ref (Slide 18): https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -06-21-23/05 -RSV -Adults -Ortega -Sanchez -508.pdf
1 GSK Phase 3 Trial; interim analysis 2023; CDC -calculated vaccine efficacy in participants ages ≥60 years
2 Pfizer Phase 3 Trial; interim analysis 2023; CDC -calculated vaccine efficacy in participants ages ≥60 years
3 Efficacy estimates are not directly comparable. Clinical trials used different outcome definitions and the follow up time in differed substantially across
trials. Further, efficacy estimates are associated with substantial uncertainty.
4 CDC -calculated VE against medically -attended RSV acute respiratory illness (ARI)
5 CDC -calculated VE against medically -attended RSV lower respiratory tract disease (LRTD)
6 CDC -calculated VE against medically -attended RSV lower respiratory tract illness (LRTI) with at least 3 lower respiratory sympto ms10
Weekly rates of RSV -associated hospitalization,* all ages,
RSV -NET, October 2018 –February 2024
*RSV -NET hospitalization data are preliminary and subject to change as more data becomes available.
Rates have not been adjusted for testing practices and underestimate actual rates of RSV -associated hospitalizations, as not all  people hospitalized with respiratory illness are
tested for RSV. In addition, clinician -directed RSV testing practices may have changed over time and may differ by disease sever ity, age, and/or racial and ethnic group of
patients; trends in RSV -associated hospitalization rates across seasons should be interpreted with caution.
For more information on RSV -NET, please visit https://www.cdc.gov/rsv/research/rsv -net/index.html . 2018 -192019 -20
2020 -212021 -222022 -23
2023 -24
0123456
40414243444546474849505152123456789101112131415161718192021222324252627282930313233343536373839
Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug SepWeekly RSV -associated hospitalizations
per 100,000 population
Month and MMWR Week
11
▪Clinical trials of both vaccines under -enrolled adults 75 years
and older and were under -powered to estimate vaccine
efficacy in this age subgroup.
▪Aging results in lowered immune responsiveness
characterized by impairments in both innate and adaptive
immunity (immune senescence).*
▪Adults 75 years and older might experience reduced VE
against all outcomes, compared with adults ages 60 –74 years.
▪There are no data yet available from post -licensure
observational effectiveness studies to estimate protection
among adults aged ≥75 years.Inputs: Vaccine Efficacy (VE), sensitivity analysis
Assumed VE among adults aged ≥75 years is reduced by half , compared with adults aged 60 –74 years
*Stephens LM, Varga SM. Considerations for a Respiratory Syncytial Virus Vaccine Targeting an Elderly Population. Vaccines (B asel). 2021 Jun 9;9(6):624.
https://doi.org/10.3390/vaccines9060624
12
Outcome (RSV -Associated) Arexvy , GSK1
VE (95% CI)Abrysvo, Pfizer2
VE (95% CI)
Season 1
(months 0 -7
post -injection)Season 2
(months 13 -18
post -injection )3Season 1
(months 0 -7
post -injection)Season 2
(months 8 -14
post -injection )3
Outpatient visits3
Trial efficacy against medically -attended
RSV ARIAges 60 –74 yrs:
79.0%
Ages ≥75 yrs:
39.5%Ages 60 –74 yrs:
27.8%
Ages ≥75 yrs:
13.9%Ages 60 –74 yrs:
65.2%
Ages ≥75 yrs:
32.6%Ages 60 –74 yrs:
55.0%
Ages ≥75 yrs:
27.5%
Hospitalizations, ICU Admissions,
and In -hospital Deaths
Trial efficacy against medically -attended
RSV LRTD/LRTIAges 60 –74 yrs:
87.5%4
Ages ≥75 yrs:
43.8%Ages 60 –74 yrs:
52.9%4
Ages ≥75 yrs:
26.5%Ages 60 –74 yrs:
84.6%5
Ages ≥75 yrs:
42.3%Ages 60 –74 yrs:
75.0%5
Ages ≥75 yrs:
37.5%Inputs: Vaccine Efficacy (VE), sensitivity analysis
13Point estimates were used in this analysis. Uncertainty in vaccine efficacy was not incorporated into uncertainty in estimate d preventable outcomes.
Ref (Slide 18): https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -06-21-23/05 -RSV -Adults -Ortega -Sanchez -508.pdf
1 GSK Phase 3 Trial; interim analysis 2023; CDC -calculated vaccine efficacy in participants ages ≥60 years
2 Pfizer Phase 3 Trial; interim analysis 2023; CDC -calculated vaccine efficacy in participants ages ≥60 years
3 Efficacy estimates are not directly comparable. Clinical trials used different outcome definitions and the follow up time in differed substantially across trials. Further, efficacy
estimates are associated with substantial uncertainty.
4 CDC -calculated VE against medically -attended RSV acute respiratory illness (ARI)
5 CDC -calculated VE against medically -attended RSV lower respiratory tract disease (LRTD)
6 CDC -calculated VE against medically -attended RSV lower respiratory tract illness (LRTI) with at least 3 lower respiratory sympto ms
Results: Estimated Benefits
Per 1 million vaccine doses administered
Estimated RSV -Associated Outcomes* Preventable over 2 RSV Seasons
per 1 Million Vaccine Doses Administered to Adults Aged ≥60 Years
*Ranges of preventable outcomes were calculated using published 95% confidence intervals (outpatient only) and adjusted 95% confidence interval of
RSV-associated incidence of the outcome observed in RSV -NET. Uncertainty in vaccine efficacy was not incorporated into ranges of  preventable outcomes.120 450 2,400
 -  1,000  2,000  3,000  4,000  5,000140 520 2,700
 -  1,000  2,000  3,000  4,000  5,000Outpatient visits
Hospitalizations
ICU Admissions
In-hospital Deaths//23,000Arexvy  (GSK) Abrysvo  (Pfizer)
\\26,000
15
Estimated RSV -Associated Outcomes* Preventable over 2 RSV Seasons
per 1 Million Vaccine Doses Administered,  Arexvy  (GSK)
350 870 6,000
170 660 3,200
86 390 1,900
66 340 1,500
41 260 1,100
 -  1,000  2,000  3,000  4,000  5,000  6,000  7,000  8,000  9,000  10,00060-64 years
65-69 years
70-74 years
75-79 years
≥80 yearsHospitalizations
ICU Admissions
In-Hospital Deaths
*Ranges of preventable outcomes were calculated using published 95% confidence intervals (outpatient only) and adjusted 95% confidence interval of
RSV-associated incidence of the outcome observed in RSV -NET. Uncertainty in vaccine efficacy was not incorporated into ranges of  preventable outcomes.16
//  18,000
//  24,000
//  24,000
//  24,000
//  24,000
//  23,000
175 435 3,000
85 330 1,600
86 390 1,900
66 340 1,500
41 260 1,100
 -  1,000  2,000  3,000  4,000  5,000  6,000  7,000  8,000  9,000  10,00060-64 years
65-69 years
70-74 years
75-79 years
≥80 yearsHospitalizations
ICU Admissions
In-Hospital DeathsSensitivity analysis:
Vaccine efficacy reduced by
half among adults ≥75 yearsEstimated RSV -Associated Outcomes* Preventable over 2 RSV Seasons
per 1 Million Vaccine Doses Administered,  Arexvy  (GSK)
*Ranges of preventable outcomes were calculated using published 95% confidence intervals (outpatient only) and adjusted 95% confidence interval of
RSV-associated incidence of the outcome observed in RSV -NET. Uncertainty in vaccine efficacy was not incorporated into ranges of  preventable outcomes.17
Estimated RSV -Associated Outcomes* Preventable over 2 RSV Seasons
per 1 Million Vaccine Doses Administered,  Abrysvo  (Pfizer)
Hospitalizations
ICU Admissions
In Hospital Deaths
400 990 6,800
200 750 3,600
98 440 2,200
75 380 1,700
46 300 1,200
0 1,000 2,000 3,000 4,000 5,000 6,000 7,000 8,000 9,000 10,00060-64 years
65-69 years
70-74 years
75-79 years
≥80 years
*Ranges of preventable outcomes were calculated using published 95% confidence intervals (outpatient only) and adjusted 95% confidence interval of
RSV-associated incidence of the outcome observed in RSV -NET. Uncertainty in vaccine efficacy was not incorporated into ranges of  preventable outcomes.18
Hospitalizations
ICU Admissions
In Hospital Deaths
200 495 3,400
100 375 1,800
98 440 2,200
75 380 1,700
46 300 1,200
0 1,000 2,000 3,000 4,000 5,000 6,000 7,000 8,000 9,000 10,00060-64 years
65-69 years
70-74 years
75-79 years
≥80 yearsSensitivity analysis:
Vaccine efficacy reduced by
half among adults ≥75 yearsEstimated RSV -Associated Outcomes* Preventable over 2 RSV Seasons
per 1 Million Vaccine Doses Administered,  Abrysvo  (Pfizer)
*Ranges of preventable outcomes were calculated using published 95% confidence intervals (outpatient only) and adjusted 95% confidence interval of
RSV-associated incidence of the outcome observed in RSV -NET. Uncertainty in vaccine efficacy was not incorporated into ranges of  preventable outcomes.19
▪23,000 (17,000 –28,000)
▪2,400 (1,800 –3,700)
▪450 (350 –690)
▪120 (94 –190)Summary:
Estimated preventable RSV -associated outcomes varies by age and incidence of the outcome
Arexvy  (GSK)
▪26,000 (19,000 –32,000)

▪2,700 (2,100 –4,200)
▪520 (400 –780)
▪140 (110 –210)Abrysvo  (Pfizer)
Outpatient visits
Hospitalizations
ICU admissions
In-hospital deaths▪Estimated number of outcomes preventable over 2 RSV seasons
per 1 million doses administered were similar between vaccine products:
Ranges of preventable outcomes were calculated using published 95% confidence intervals (outpatient only) and adjusted 95% confidence interval of R SV-
associated incidence of the outcome observed in RSV -NET. Uncertainty in vaccine efficacy was not incorporated into ranges of preventable outcomes.20
Potential Risk of Guillain -Barre syndrome (GBS)
Per 1 million vaccine doses administered
▪Claims -based ascertainment of GBS events using administrative data
–GBS cases observed after RSV vaccination during a 42-day risk interval2, adjusted for delays in claims data
–Adjustment for positive -predictive value of diagnostic codes in identifying chart -confirmed GBS
▪GSK Arexvy : 10 GBS cases (95% CI 2 –18) per 1 million doses administered
▪Pfizer Abrysvo : 25 GBS cases (95% CI 7 –43) per 1 million doses administered
▪Expected cases based on historical GBS background rate from 2022:
–5 GBS cases per 1 million doses administered3
–Historical background rate may not be applicable to persons electing to receive RSV vaccination using
shared clinical decision -making. On average, recipients of each of the two vaccines may be at different
baseline risk of GBS. More robust analysis, such as a self -controlled case series, is needed to confirm and
quantify a risk of Guillain -Barre syndrome after RSV vaccination.FDA active surveillance through partnership with CMS,
Medicare beneficiaries ages ≥65 years1, May –December 2023
Abbreviations: CI = confidence interval, CMS = Centers for Medicare & Medicaid Services, FDA = U.S. Food and Drug Administrat ion, GBS = Guillain -Barre syndrome
1.Must have been enrolled in Medicare Parts A, B and D. Must not have had a diagnostic code for GBS in the 365 days preceding v accination.
2.Due to delays in claims data, not all participants have accrued 42 days of effective follow up time. GBS observation rates pe r 1 million doses over a 21-day risk interval
were also calculated ( GSK Arexvy : 5 cases [95% CI 1 –9], Pfizer Abrysvo : 13 cases [95% CI 3 –22]).
3.The lower and upper bounds of the 95% confidence interval for the expected cases both round to 5. With additional precision: 5.06 expected GBS cases (95% CI 4.76 –
5.38) per 1 million doses administered to adults ages 65 years and older. 22
Estimated Benefits and
Potential Risk
Per 1 million vaccine doses administered
Per 1 Million Vaccine Doses Administered to Adults Aged ≥60 Years:
1.Range of outcomes avertable was calculated using published 95% confidence intervals (outpatient only) and adjusted 95% confid ence interval of RSV -associated incidence of the outcome observed in RSV -NET
2.Includes GBS cases in a 42 -day risk interval post -RSV-vaccination, adjusted for claims delay, a mong beneficiaries ≥65 with Parts A, B, and D coverage who did not have a GBS claim in the 365 days before
vaccination. Rates of GBS identified by inpatient claims data are decreased by 29% to account for the positive predictive val ue of diagnostic codes in identifying chart -confirmed GBS cases.
3.Background GBS rate (4.4 cases per 100,000 person -years) from 2022 CMS data among Medicare beneficiaries 65 years and older with  Parts A, B, and D coverage and without a GBS claim in the 365 days
before January 1, 2022. Rates of GBS identified by inpatient claims data are decreased by 29% to account for the positive pre dictive value of diagnostic codes in identifying chart -confirmed GBS cases.Estimated RSV -Associated Outcomes1 Preventable over 2 RSV Seasons  vs. potential cases of GBS
(positive predictive value -adjusted  rate of GBS claims in FDA -CMS partnership data, 42 -day risk interval2)
By comparison, 5 GBS cases would be expected from background over the 42 -day risk interval3.
Historical background rate may not apply to adults electing to receive RSV vaccination using shared clinical decision -making. On  average, recipients of each of the two
vaccines may be at different baseline risk of GBS. More robust analysis, such as a self -controlled case series, is needed to con firm and quantify a risk of GBS.10 (95% CI  2–18) cases of GBS 25 (95% CI 7–43) cases of GBS
1.Range of outcomes avertable was calculated using published 95% confidence intervals (outpatient only) and adjusted 95% confid ence interval of RSV -associated incidence of the outcome observed in RSV -NET
2.Includes GBS cases in a 42 -day risk interval post -RSV-vaccination, adjusted for claims delay, a mong beneficiaries ≥65 with Parts A, B, and D coverage who did not have a GBS claim in the 365 days before
vaccination. Rates of GBS identified by inpatient claims data are decreased by 29% to account for the positive predictive val ue of diagnostic codes in identifying chart -confirmed GBS cases.
3.Background GBS rate (4.4 cases per 100,000 person -years) from 2022 CMS data among Medicare beneficiaries 65 years and older with  Parts A, B, and D coverage and without a GBS claim in the 365 days
before January 1, 2022. Rates of GBS identified by inpatient claims data are decreased by 29% to account for the positive pre dictive value of diagnostic codes in identifying chart -confirmed GBS cases.Estimated RSV -Associated Outcomes1 Preventable over 2 RSV Seasons  vs. potential cases of GBS
(positive predictive value -adjusted  rate of GBS claims in FDA -CMS partnership data, 42 -day risk interval2)
By comparison, 5 GBS cases would be expected from background over the 42 -day risk interval3.
Historical background rate may not apply to adults electing to receive RSV vaccination using shared clinical decision -making. On  average, recipients of each of the two
vaccines may be at different baseline risk of GBS. More robust analysis, such as a self -controlled case series, is needed to con firm and quantify a risk of GBS.10 (95% CI  2–18) cases of Guillain -Barre syndromePer 1 Million GSK Arexvy  Doses Administered to Older Adults:
60–64 yrs 65–69 yrs 70–74 yrs 75–79 yrs ≥80 yrs
Hospitalizations
preventable1,100 1,500 1,900 3,200 6,000
ICU admissions
preventable260 340 390 660 870
In-hospital deaths
preventable41 66 86 170 350
25
1.Range of outcomes avertable was calculated using published 95% confidence intervals (outpatient only) and adjusted 95% confid ence interval of RSV -associated incidence of the outcome observed in RSV -NET
2.Includes GBS cases in a 42 -day risk interval post -RSV-vaccination, adjusted for claims delay, a mong beneficiaries ≥65 with Parts A, B, and D coverage who did not have a GBS claim in the 365 days before
vaccination. Rates of GBS identified by inpatient claims data are decreased by 29% to account for the positive predictive val ue of diagnostic codes in identifying chart -confirmed GBS cases.
3.Background GBS rate (4.4 cases per 100,000 person -years) from 2022 CMS data among Medicare beneficiaries 65 years and older with  Parts A, B, and D coverage and without a GBS claim in the 365 days
before January 1, 2022. Rates of GBS identified by inpatient claims data are decreased by 29% to account for the positive pre dictive value of diagnostic codes in identifying chart -confirmed GBS cases.Estimated RSV -Associated Outcomes1 Preventable over 2 RSV Seasons  vs. potential cases of GBS
(positive predictive value -adjusted  rate of GBS claims in FDA -CMS partnership data, 42 -day risk interval2)
By comparison, 5 GBS cases would be expected from background over the 42 -day risk interval3.
Historical background rate may not apply to adults electing to receive RSV vaccination using shared clinical decision -making. On  average, recipients of each of the two
vaccines may be at different baseline risk of GBS. More robust analysis, such as a self -controlled case series, is needed to con firm and quantify a risk of GBS.25 (95% CI  7–43) cases of Guillain -Barre syndromePer 1 Million Pfizer Abrysvo  Doses Administered to Older Adults:
60–64 yrs 65–69 yrs 70–74 yrs 75–79 yrs ≥80 yrs
Hospitalizations
preventable1,200 1,700 2,200 3,600 6,800
ICU admissions
preventable300 380 440 750 990
In-hospital deaths
preventable46 75 98 200 400
26
▪We assumed optimal timing of vaccination immediately before onset of RSV season.
▪We assumed that the real -world vaccine effectiveness is equal to point estimate of vaccine
efficacy observed in the phase 3 clinical trials.
–Assumed vaccine effectiveness against hospitalization was equal to vaccine efficacy against medically
attended RSV -associated lower respiratory tract disease from clinical trials
–Did not incorporate uncertainty in trial efficacy estimates. However, in preliminary analyses, uncertainty
in RSV incidence resulted in wider ranges of preventable outcomes than uncertainty in efficacy.
▪Clinical trials were performed largely in community dwelling older adults and may not be
generalizable to all adults 60+ in the U.S.
▪RSV -NET represents ~9% of the United States and hospitalization rates observed in RSV -NET
may not be generalizable to the U.S.
▪Benefits of a single dose of RSV vaccination may continue to accrue beyond 2 years.
▪RSV -NET does not currently estimate out -of-hospital deaths, resulting in an under -estimate of
potentially vaccine -preventable deaths.
▪Benefits may be greater for subgroups of adults at increased risk of severe RSV illness.Limitations (estimation of benefits)
27
▪GBS rates were calculated using a small number of events observed after RSV
vaccination, resulting in high uncertainty.
▪A background rate of GBS was not subtracted from the observed rate.
–The historical background rate from CMS used as a comparator may not apply to adults receiving RSV
vaccination using shared clinical decision -making; subject to confounding and bias.
▪Older adults receiving each of the two vaccine products may have different prevalence
of chronic medical conditions or other risk factors and may therefore have different
baseline risk of GBS.
▪GBS was identified by diagnostic codes in administrative data and may be subject to
coding errors.
▪Not all cases of GBS occurring after RSV vaccination may have received a diagnostic
code.Limitations (estimation of risk)
28
▪From a population perspective, the estimated benefits of RSV vaccination outweigh
the potential risk of GBS in adults 60 years and older.
▪Estimated benefits of RSV vaccination vary by age group and RSV incidence.
▪Estimated benefits likely also vary by individual -level risk of severe RSV disease and by
timing of vaccination relative to the RSV season.
▪There is substantial uncertainty in estimates of both benefit and risk.
▪The benefit and risk assessment will be updated as additional data become available:
–Results from additional vaccine safety studies
–Additional efficacy follow -up time from clinical trials
–Vaccine effectiveness from post -licensure observational studies, including effectiveness against more
severe clinical outcomes
–RSV disease burden among subgroups of older adults at increased risk of severe RSV diseaseSummary
29
▪Lauren Roper
▪Amadea Britton
▪Dani Moulia
▪Megan Wallace
▪Katherine Fleming -Dutra
▪Fiona Havers
▪Michael Whitaker
▪John Su
▪Karen Broder▪Eric Weintraub
▪David Shay
▪Anne Hause
▪Pedro Moro
▪Tom Shimabukuro
▪Patricia Lloyd
▪Richard Forshee
▪Steven AndersonAcknowledgements
30
For more information, contact CDC
1-800 -CDC -INFO (232 -4636)
TTY:  1 -888 -232-6348    www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official
position of the Centers for Disease Control and Prevention.
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.

Summary: Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. RSV Vaccination in Older Adults: Benefit -Risk Discussion Michael Melgar , MD Lauren Roper, MPH Advisory Committee on Immunization Practices February 29, 2024 There are…


08 RSV Adults Britton 508

Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.
RSV Vaccination in Older Adults:
Work Group Interpretations
Amadea Britton, MD
Advisory Committee on Immunization PracticesFebruary 29, 2024
2This includes follow- up of the implementation and experience of the current shared
clinical decision -making recommendation, understanding uptake of RSV vaccines
across age and demographic groups, consideration of new vaccine products , and
potential expansion of RSV vaccines to younger age groups .
However, the Work Group believes that contextualization and understanding of
current safety data are paramount in determining future preferred policy options
for the adult RSV vaccination program.
Therefore, today’s Work Group interpretations focus primarily on the safety and benefit/risk data reviewed today.
We will then briefly review the proposed roadmap for expected future policy decisions. First, the Work Group would like to acknowledge that there are multiple
concurrent policy issues to consider in the older adult RSV vaccine
landscape.
3Summarize Work Group interpretations of current RSV vaccine safety surveillance
data and the balance of estimated benefits vs potential risks associated with use of RSV vaccines in adults ages 60 years and older
Share updated clinical considerations incorporating timing of RSV vaccine administration in shared clinical decision- making
Update on plans for future policy considerations in the older adult RSV vaccine program Objectives
Work Group interpretation of current RSV
vaccine safety data and benefit/risk of RSV
vaccination in adults ages 60 years and older
5Due to the small number of cases, it was unclear whether the cases observed in the trials represented
a genuine association between RSV vaccination and risk of GBS or whether the cases observed in the
trials were due to chance alone.
The potential for increased risk of GBS was discussed extensively during deliberations for the older
adult recommendation. ACIP concluded that the estimated benefits of RSV vaccination outweighed
potential risks.
However, ACIP recommended RSV vaccines be given using shared clinical decision- making with a
healthcare provider. The shared clinical decision- making recommendation was intended to
facilitate individualized risk -benefit discussions, acknowledging that the balance of risks and
benefits may depend on the characteristics of the individual vaccine recipient.
Clinical guidance advised that a patient’s risk for severe RSV -associated disease should be the core of
shared clinical decision -making, with vaccination targeted to those who are at highest risk for severe
RSV disease and therefore most likely to benefit from vaccination.The initial RSV vaccine recommendation for adults 60 years and older was made in
the setting of a small number of cases of inflammatory neurologic events (particularly GBS) observed in the clinical trials for both GSK and Pfizer’s RSV vaccines for older adults.
6February May June NovemberDecember -
JanuaryFebruaryRSV older adult vaccine safety surveillance timeline
Abbreviations: ACIP = Advisory Committee on Immunization Practices, CISA = Clinical Immunization Safety Assessment Project, C MS = Centers for Medicare & Medicaid
Services, FDA= Federal Drug Administration, GBS = Guillain -Barre syndrome, RSV = respiratory syncytial virus, VAERS = Vaccine Ad verse Event Reporting System, VRBPAC=
Vaccines and Related Biological Products Advisory Committee Meeting; VSD = Vaccine Safety Datalink
*CISA is covered by a CDC Assurance of Confidentiality 2023 2024
ACIP votes to
recommend RSV vaccination for adults aged  ≥60 years , using
shared clinical decision- making. Small number of GBS cases observed in the clinical trials in adults aged  ≥60 years for GSK
and Pfizer RSV vaccines. Safety data shared at FDA VRBPAC
and ACIP meetings.VAERS scientists
continued monitoring and verifying GBS
reports; CISA continued review.First preliminary safety surveillance data available from CDC V -
safe, CDC VSD and FDA
CMS. Number of GBS cases in VAERS raised possibility
that cases observed might be above expected background rate. CDC
organized CISA calls with
clinical experts inneurology to
review cases of GBS
reported to VAERS.*RSV vaccines licensed for use in adults aged ≥60 years. Information on trial GBS cases included in product package inserts. Safety
monitoring commences immediately post -
licensure.
7Today, CDC’s Immunization Safety Office and FDA shared
preliminary data from multiple surveillance systems: VAERS, VSD, and the FDA -CMS partnership.
The data from these systems have been shared as near real -time
findings and allow us to be immediately responsive to early signals.
Together, the data support a potential increased risk for GBS after RSV vaccination among adults aged ≥60 years .
However, due to uncertainty and limitations in these early data, there is currently insufficient evidence to confirm whether RSV
vaccination is associated with increased risk for GBS in older
adults, or to estimate the magnitude of any increase in GBS risk after RSV vaccination.
Assessing the risk for GBS following receipt of the RSV vaccine among older adults in more robust analyses in active vaccine safety surveillance systems will be crucial and is underway. Surveillance with a focus on early detection of increased risk
of GBS after RSV vaccination began immediately post -
licensure.
+
8Any increase in potential risk of GBS should be placed in the context of the
benefits of RSV vaccination.
Earlier in this session, we summarized what we know about the estimated benefits of RSV vaccine and compared that to what we know currently about potential risk of GBS. This benefit- risk analysis showed that:
–From a population perspective, the estimated benefits of RSV vaccination outweigh  the estimated
risks for adults 60 years and older.
–Benefits of RSV vaccination vary by age group and RSV incidence.
–Benefits likely also vary by individual -level risk  of severe RSV disease and by timing of vaccination
relative to the RSV season.
We also saw data demonstrating that adults with certain chronic conditions are at increased risk of severe RSV disease, even at younger ages. How do these new data impact the Work Group’s thinking about RSV
vaccine for older adults?
9The Work Group also reviewed examples from other licensed and recommended
vaccines of benefit -risk considerations in practice.
Seasonal influenza vaccine: routine annual influenza vaccination is recommended for all persons aged
≥6 months who do not have contraindications. Adults aged ≥65 years  should preferentially receive high -
dose, recombinant, or adjuvanted influenza vaccines.1
–The data on the association between GBS and seasonal influenza vaccination are variable and
inconsistent across influenza seasons. If there is an increased risk of GBS following influenza vaccination
it is small, on the order of 1–2 additional cases per million doses of influenza vaccine administered.
Studies also suggest that it is more likely that a person will get GBS after getting the influenza disease
than after influenza vaccination.2
1. Grohskopf LA, et al. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on  Immunization Practices —  United States, 2023 –24 Influenza Season.
MMWR Recomm  Rep 2023;72(No. RR -2):1 –25. http://dx.doi.org/10.15585/mmwr.rr7202a1
2. Vellozzi C, Iqbal S, and Broder K. Guillain -Barré Syndrome, Influenza, and Influenza Vaccination: The Epidemiologic Evidence, Clinical Infectious Diseases , Volume 58, Issue 8, 15 April 2014, Pages 1149 –
1155, https://doi.org/10.1093/cid/ciu005 .9
10Summary of RSV and Influenza disease -associated hospitalizations, estimated vaccine-
avertable disease hospitalizations, and potential vaccine -associated GBS risk
Disease -associated
hospitalizations per 1 million
population per year in the U.S.Estimated disease -associated
hospitalizations avertable per 1
million persons vaccinatedPotential vaccine -associated GBS
cases per1 million persons vaccinated
RSV1,700 – 2,800
1
among adults ages 65 and olderOver two RSV seasons, among adults ages 60 and olderGSK: 2,400 (1,800 – 3,700)
2
Pfizer: 2,700 (2,100 – 4,200)2GSK: 10 (2 –18) cases3
Pfizer: 25 (7 –43) cases3
Not adjusted for background rate of GBS
Expected from background rate :
5cases of GBS (95% CI: 4.8,
5.4) per 1million doses given
4
Influenza3,200 – 9,2005
among adults ages 65 and olderOver one influenza season,
among adults ages 65 and older
2,000 (300 –  5,500)6Variable and inconsistent across
influenza seasons. If there is an
increased risk, it is small: ~1–2
additional  cases per million doses
given7,8
1. CDC RSV -NET data 2016– 2020, 2022 –2023 (unpublished)
2. Unpublished benefit/risk analysis presented at this ACIP meeting (February 2024).
3. FDA analysis of CMS data. Includes GBS cases in a 42 -day risk interval post -RSV -vaccination, adjusted for claims delay, among be neficiaries 65 and older with Parts A and B coverage who did not have a GBS claim in the 365 days before vaccination. These are rates of GBS identified by inpatient claims data and are decreased
by 29% to account for the positive predictive value of diagnostic codes in identifying chart -confirmed GBS cases. A GBS backgrou nd rate is not subtracted from these rates.
4. FDA analysis of CMS data. Background rate based on GBS cases observed per 100,000 person -years among Medicare beneficiaries 65 and older with Parts A and B coverage in 2022. Beneficiaries must not have had an International Classification of Diseases, 10 th revision, clinical modification (ICD -10-CM) diagnostic code
for GBS in the 365 days preceding January 1, 2022. Rate per 100,000 person -years applied used to estimate cases expected over 42 -day follow -up for 1 million persons.
5. CDC Influenza Burden 2016– 2020, 2022 –2023: https://www.cdc.gov/flu/about/burden/past -seasons.html
6. Ellen KD, Gebremariam  A, Rose A, et al. Cost -effectiveness of routine annual influenza vaccination by age and risk status. Vaccine: 41 (29): 4239- 424 8. 2023. https://doi.org/10.1016/j.vaccine.2023.04.069
7. Vellozzi C, Iqbal S, and Broder K. Guillain -Barré Syndrome, Influenza, and Influenza Vaccination: The Epidemiologic Evidence, Clinical Infectious Diseases , Volume 58, Issue 8, 15 April 2014, Pages 1149 –1155, https://doi.org/10.1093/cid/ciu005 .
8. Committee to Review Adverse Effects of Vaccines; Institute of Medicine; Stratton K, Ford A, Rusch  E, et al., editors. Adverse Effects of Vaccines: Evidence and Causality. Washington (DC): National Academies Press (US); 2011  Aug 25. 6, Influenza Vaccine. Available from: https://www.ncbi.nlm.nih.gov/books/NBK190013/
Influenza Vaccine - Adverse Effects of Vaccines - NCBI Bookshelf (nih.gov).10
11The Work Group also considered examples from other licensed and recommended
vaccines of benefit -risk consideration in practice.

–
Recombinant zoster vaccine: CDC recommends two doses of recombinant zoster vaccine (RZV,
Shingrix) 2 –6 months apart for adults aged ≥50 years and for adults aged ≥19 years who are or will be
immunocompromised, for prevention of herpes zoster (shingles) and related complications .3,4
–3-6 additional cases of GBS projected per million RZV vaccinated .5
–Risk- benefit analysis incorporated available data on risk of GBS following zoster disease and vaccination with RZV
3. Dooling KL, et al. Recommendations of the Advisory Committee on Immunization Practices for Use of Herpes Zoster Vaccines. MMW R Morb  Mortal Wkly  Rep 2018;67:103 –108. http://dx.doi.org/10.15585/mmwr.mm6703a5
4. Anderson TC, et al. Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged ≥19 Years: Recommendations of the Advi sory Committee on Immunization Practices — United States, 2022. MMWR Morb  Mortal
Wkly  Rep 2022;71:80 –84. http://dx.doi.org/10.15585/mmwr.mm7103a2
5. Janusz CB, et al. Projected risks and health benefits of vaccination against herpes zoster and related complications in US ad ults. Hum Vaccin  Immunother. 2022 Nov 30;18(5):2060668.
https://doi.org/10.1080/21645515.2022.206066811
12Experience with recombinant zoster vaccine (Shingrix)
In 2019, a statistical safety signal for GBS following
recombinant zoster vaccine was identified in VSD; evidence was insufficient to confirm the initial signal.
FDA, CDC, and collaborators conducted additional extensive safety assessments.
1,2
Using data from this safety surveillance, a formal
analysis evaluating health risks and benefits was
undertaken. Epidemiologic data suggesting a potentially elevated risk of GBS following an
episode of herpes zoster (HZ) in the U.S. adult
population was also included.
3
In this analysis , benefits were assumed to accrue
over a period of 20 years after vaccination.
Vaccination averted 43,000– 63,000 cases of HZ,
including GBS complications, per million
vaccinated per 10-year age cohort compared to 3 –
6 additional cases of GBS  projected per million
vaccinated with recombinant zoster vaccine in the same population.
4
Importantly, RSV disease is not directly comparable to herpes zoster disease.
* Projected number of averted cases of postherpetic neuralgia and ocular complications have been rounded to two significant f igures. For exact numbers see Janusz et al. below.
1. Goud R, et al. Risk of Guillain -Barré Syndrome Following Recombinant Zoster Vaccine in Medicare Beneficiaries. JAMA Intern Med. 2021 Dec 1;181(12):1623 -1630. doi: 10.1001/jamainternmed.2021.6227.
2. Nelson JC, et al. Active Postlicensure  Safety Surveillance for Recombinant Zoster Vaccine Using Electronic Health Record Data. Am J Epidemiol. 2023 Feb 1;192(2):205 -216. doi: 10.1093/ aje/kwac170.
3. Anderson TC, et al. Risk of Guillain -Barré syndrome following herpes zoster, United States, 2010 -2018. Hum Vaccin  Immunother. 2021 Dec 2;17(12):5304 -5310. doi : 10.1080/21645515.2021.1985890.
4. Janusz CB, et al. Projected risks and health benefits of vaccination against herpes zoster and related complications in US ad ults. Hum Vaccin  Immunother. 2022 Nov 30;18(5):2060668. https://doi.org/10.1080/21645515.2022.2060668Age group (years)Postherpetic neuralgiaOcular complicationsDeaths Incremental
GBS increase Notes
50-59 5,500 4,300 47
3 – 6 • 20-year time horizon
• Incremental GBS increase subtracts background rate of
GBS and HZ -
associated GBS
averted
• Outcomes averted per million 1 -dose or
2-dose series60-69 9,400 5,500 62
70-79 12,000 5,700 171
80-89 12,000 5,200 155
90-99 11,000 3,900 116Projected cases* of postherpetic neuralgia, ocular complications, and
death averted through recombinant  zoster vaccine per million vaccinated,
compared to incremental GBS increase per million412
13Based on this review of currently available data, the Work Group
continues to believe that the estimated benefits of RSV
vaccination outweigh potential risks when vaccination is
implemented using the current recommendation: Adults aged
≥60 years may receive RSV vaccination, using shared clinical decision-making.
14However, the Work Group expressed that
estimated benefits most clearly outweigh
potential risks among adults 60 and older who are at increased risk of severe RSV disease.
This includes a dults who are 60 and older with
chronic medical conditions such as chronic lung
diseases, heart failure, immune compromise, those of more advanced age, and those living in long -term care facilities (e.g., nursing homes).  A majority of Work Group members expressed that the balance of
estimated benefits outweighed potential risks for all adults 60 and older.

15Estimated age distribution of national RSV -associated hospitalizations, ICU admissions, and in-
hospital deaths among adults ≥18 years, RSV -NET, 2022 –2023, compared with U.S. population
Unpublished data. Underlying rates are adjusted using multipliers for the frequency of RSV testing during each season and for  the sensitivity of RSV diagnostic tests. Estimates
from 2022- 2023 are preliminary. These estimates use the same multipliers as for 2019 -2020.
*As of 2022. https://www.census.gov/popclock/  42.9%
37.1%
58.0%
9.2%23.9%
26.8%
22.8%
13.0%20.4%
22.6%
11.3%
24.1%12.8%
13.6%
7.9%
53.7%
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%Hospitalizations
ICU admissions
In-hospital deaths
U.S. Adult Population*≥75 65-74 50-64 18-49
U.S. Adult Population *Age group, years:
16Underlying medical conditions* among non- pregnant adults ≥18 years with RSV -
associated hospitalizations — RSV -NET, 2014 –2015 to 2017 –2018 and 2022 –2023
Major underlying condition categories Unweighted
N=7,479Weighted
%
Cardovascular disease (overall) 5,141 57.4
Obesity 2,798 39.0
Diabetes 2,484 34.1
COPD 2,248 31.4
Heart failure 1,984 28.0
Chronic kidney disease 2,003 27.0
Asthma 1,789 24.0
Coronary artery disease (includes CABG, MI) 1,718 24.0
Neurologic condition 1,628 22.6
Immune compromised 1,567 20.8
Chronic metabolic disease, not including diabetes 1,417 19.3
Other chronic lung disease 995 17.1
Chronic liver disease 538 7.2
Autoimmune/inflammatory disease 310 4.5
Blood disorders 287 4.194.3% of adults ≥18
years with RSV -
associated hospitalization
had at
least one underlying medical condition
:
•31.4%: 1– 2 conditions
•62.9%: ≥3 conditions
*Clinical data, including underlying medical conditions, were collected for all patients with laboratory -confirmed RSV hospitalizations during the 2014 –2015 to 2017– 2018 seasons, and for an
age- and site -stratified random sample of patients with laboratory -confirmed RSV hospitalizations during the 2022 –2023 season. Data are presented as unweighted case counts and weighted
percentages that were weighted for the probability of selection.
17For these adults, the benefit from RSV vaccination may be
lower.
However, the Work Group felt that  these adults might still
benefit from vaccination depending on their individual situation and the decision to get vaccinated should be based
on discussion with a healthcare provider .
The shared clinical decision- making recommendation
continues to support this flexibility. The Work Group noted that for older adults who do not have any chronic
medical conditions  and who do not live in long -term care facilities , the risk
of severe RSV disease is lower.
18Providers will need support in appropriately framing shared clinical
decision -making discussions with their older adult patients.
Providers may need additional communications materials clarifying which of their patients aged ≥60 years are at increased risk of severe RSV
disease and would benefit most from vaccination.
Providers may need more materials to support discussing current safety
data. The Work Group also stresses that discussion of benefits vs
potential risks should remain the core of shared clinical decision -
making.
19Uncertainty in estimates of risk
–Estimated risk is uncertain and confidence intervals are wide
–Among adults electing to receive RSV vaccine, background rates of GBS are uncertain
•Adults receiving RSV vaccine may differ from those who do not choose vaccines in underlying health status or
other ways that could impact background risk of GBS
•It is unclear if recipients of different RSV vaccine products may also differ in ways that could affect their underlying risk of GBS independent of RSV vaccination
Uncertainty in estimates of benefit
–Although estimated benefits are based on the best available data, we do not yet have estimates of
real -world vaccine effectiveness against RSV -associated hospitalization and death
–The extent to which effectiveness will extend to older adults at highest risk of severe RSV disease
(those aged ≥75 years, those who are frail, those with immune compromise) is also unknown
There may be other important sources of uncertainty
–What do we need to understand about coadministration of RSV vaccine with other recommended
vaccines?
–Is RSV disease itself associated with a risk of GBS? The Work Group acknowledges the challenge of multiple sources of
uncertainty.
20V-safe data monitoring ongoing
VAERS data monitoring ongoing with CISA experts reviewing selected reports
Vaccine Safety Datalink
–Rapid cycle analysis (RCA) will be performed as soon as sufficient data (plan for first RCA March 2024)
–Power may be limited, especially for Pfizer RSV vaccine
FDA -CMS partnership ongoing
–Plan for self-controlled case series as soon as sufficient follow -up time accrued
Both manufacturers (Pfizer and GSK) conducting post -marketing studies
–GSK: Sentinel system self-controlled risk interval active surveillance, final report 2031
–Pfizer: CMS claims data active surveillance, final report 2030
Will conduct more robust risk- benefit analysis once active surveillance analyses are
able to characterize risk and estimates of real- world vaccine effectiveness are
availableSafety surveillance is ongoing and new data will be shared as soon as they
become available. The preliminary data shared today are the first in what
will be a series of rigorous analyses across multiple different platforms.
Abbreviations: CISA = Clinical Immunization Safety Assessment Project, CMS = Centers for Medicare & Medicaid Services, FDA= F ederal Drug Administration, VAERS = Vaccine
Adverse Event Reporting System
21In the interim, the Work Group wishes to affirm the importance of the RSV
vaccination program. RSV is a disease that causes significant morbidity
and mortality among persons across the age spectrum.
The Work Group is cognizant that premature changes in the RSV
vaccination program have the potential to limit access to RSV vaccine.
CDC and the Work Group are committed to incorporating what we are learning from post -licensure data in a transparent way that ensures
safety for the public and clarity for providers.CDC and the Adult RSV Work Group will be engaged in ongoing assessment. Future older adult RSV policy will be responsive to what is learned over the coming months.
Work Group considerations on timing of
RSV vaccination for adults ages 60 years and older
231.RSV seasonality had been disrupted by the COVID -19 pandemic. Based on the two
preceding RSV seasons (2021 -2022 and 2022 -2023), it was not clear when RSV
circulation might start, peak, and decline . Therefore, it was also unclear when to
time RSV vaccination to optimize benefit to an individual. In June 2023, the decision to recommend year -round RSV
vaccination was based on 3 considerations:
24National weekly* RSV percent positivity of PCR results,
NREVSS July 2016 –June 2023
*All results presented from nucleic acid amplification tests which represent >90% of the diagnostic tests reported to NREVSS.
The last three weeks of data may be less complete. NREVSS is an abbreviation for the National Respiratory and Enteric Virus Surv eillance System.
For more information on NREVSS, please visit www.cdc.gov/surveillance/nrevss .
RSV: Respiratory Syncytial Virus. Types A and B are reported but not shown separately in this report.
Results are crude, and therefore may differ from smoothed results reported online. 2016- 20,
pre-COVID -19
2020- 212021- 222022- 23
02468101214161820
2728293031323334353637383940414243444546474849505152123456789101112131415161718192021222324252627
Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun JulPercent Positive
Month and MMWR Week
251.
2.Clinical trial data indicated that both GSK and Pfizer RSV vaccines offered protection
for at least two RSV seasons. Therefore, regardless of when someone received a dose of RSV vaccine it would be expected to protect the recipient at least through the upcoming RSV season. In June 2023, the decision not to specify seasonal
administration of RSV vaccine was based on 3 considerations:
261.
2.
3.There were limited data available to understand if (or when) revaccination would be
beneficial. Not having a seasonal end to administration offered maximum flexibility and opportunity for people to receive protection for the next season. In June 2023, the decision not to specify seasonal
administration of RSV vaccine was based on 3 considerations:
27National weekly* RSV percent positivity of PCR results,
NREVSS July 2016 –February 2024
*All results presented from nucleic acid amplification tests which represent >90% of the diagnostic tests reported to NREVSS.
The last three weeks of data may be less complete. NREVSS is an abbreviation for the National Respiratory and Enteric Virus Surv eillance System.
For more information on NREVSS, please visit www.cdc.gov/surveillance/nrevss .
RSV: Respiratory Syncytial Virus. Types A and B are reported but not shown separately in this report.
Results are crude, and therefore may differ from smoothed results reported online. 2016- 20,
pre-COVID -19
2020- 212021- 222022- 23
2023- 24
02468101214161820
2728293031323334353637383940414243444546474849505152123456789101112131415161718192021222324252627
Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun JulPercent Positive
Month and MMWR Week
28Predictable  RSV seasonality makes it possible to anticipate the likely RSV season onset, peak,
and offset.
Maximizing benefits is also desirable as we continue ongoing safety monitoring.The Work Group concludes it is now advisable for providers and patients
to consider timing of RSV vaccination as part of shared clinical decision -
making  discussions.
For most older adults, benefits will be highest when RSV
vaccination is given in the late summer or early fall, just before
the onset of RSV season , so that vaccine recipients experience
highest protection during the times of peak RSV transmission over the fall and winter.
Because clinical trial data suggests that protection will wane over
time, vaccinating just before a season starts also maximizes
protection for subsequent seasons for which the vaccine offers
protection.
29For adults ages 60 years and older who remain unvaccinated and
who decide with their healthcare provider to get RSV vaccination,
the best time for vaccination is just before the start of the next
RSV season to maximize the benefits of the vaccine.
NOT  a transition to a formal seasonal recommendation for RSV
vaccination.
–Older adults may continue to receive RSV vaccination year -round , using
shared clinical decision -making.
–Intent is to allow providers and patients maximum flexibility. Patients with
infrequent healthcare contact may benefit from every opportunity to vaccinate.
NOT  a recommendation for annual re -vaccination.
–RSV vaccine for adults 60 and older is currently still recommended as a one -time
vaccine. What does it mean to include timing of vaccination in shared
clinical decision -making?
In most of the
United States,
RSV vaccination
will have the most
benefit if given in
late summer or
early fall.
30Mean weekly RSV percent positivity of PCR results by census region,
NREVSS*, 2015 –2019
*Data from Florida, Hawaii, and Alaska are excluded.
All results presented from nucleic acid amplification tests which represent >90% of the diagnostic tests reported to NREVSS.NREVSS is an abbreviation for the National Respiratory and Enteric Virus Surveillance System. For more information on NREVSS, please visit www.cdc.gov/surveillance/nrevss
.
RSV: Respiratory Syncytial Virus. Types A and B are reported but not shown separately in this report.
Results are crude, and therefore may differ from smoothed results reported online. Northeast
MidwestSouth
West
0%5%10%15%20%25%Percent Positive
Week ending date
31Mean weekly RSV percent positivity of PCR results by census region,
NREVSS*, 2015 –2019
*Data from Florida, Hawaii, and Alaska are excluded.
All results presented from nucleic acid amplification tests which represent >90% of the diagnostic tests reported to NREVSS.NREVSS is an abbreviation for the National Respiratory and Enteric Virus Surveillance System. For more information on NREVSS, please visit www.cdc.gov/surveillance/nrevss
.
RSV: Respiratory Syncytial Virus. Types A and B are reported but not shown separately in this report.Results are crude, and therefore may differ from smoothed results reported online. Northeast
MidwestSouth
West
0%5%10%15%20%25%
Jul-7
Jul-21
Aug-4
Aug-18
Sep-1
Sep-15
Sep-29
Oct-13
Oct-27
Nov-10Nov-24
Dec-8
Dec-22
Jan-5
Jan-19
Feb-2
Feb-16
Mar-2
Mar-16Mar-30
Apr-13Apr-27
May-11
May-25
Jun-8
Jun-22Percent Positive
Week ending dateRSV season onset varies by
region, from September to
November  in most of the
United States.
32Mean weekly RSV percent positivity of PCR results by census region,
NREVSS*, 2015 –2019
*Data from Florida, Hawaii, and Alaska are excluded.
All results presented from nucleic acid amplification tests which represent >90% of the diagnostic tests reported to NREVSS.NREVSS is an abbreviation for the National Respiratory and Enteric Virus Surveillance System. For more information on NREVSS, please visit www.cdc.gov/surveillance/nrevss
.
RSV: Respiratory Syncytial Virus. Types A and B are reported but not shown separately in this report.Results are crude, and therefore may differ from smoothed results reported online. Northeast
MidwestSouth
West
0%5%10%15%20%25%
Jul-7
Jul-21
Aug-4
Aug-18
Sep-1
Sep-15
Sep-29
Oct-13
Oct-27
Nov-10Nov-24
Dec-8
Dec-22
Jan-5
Jan-19
Feb-2
Feb-16
Mar-2
Mar-16Mar-30
Apr-13Apr-27
May-11
May-25
Jun-8
Jun-22Percent Positive
Week ending dateVaccination just prior to the
RSV season means from August to October  in most of
the United States.
33Weekly and Cumulative Projected RSV Vaccinations Administered in Retail Pharmacies by
Product, Adults 60 years and older, August 12, 2024 – February 2, 2024. Data Source: IQVIA*
*IQVIA Custom Weekly LRx; File
delivery date 2/8/24 .The weekly number of
RSV vaccine doses
administered appears
to have peaked and
now be declining.
Other upcoming policy considerations for RSV
vaccination in adults ages 60 years and older
35Additional policy issues Adult RSV Work Group plans
to address in June 2024
1.Potential FDA approval of Moderna mRNA- 1345 vaccine for use in
adults aged ≥60 years
2.Potential FDA approval of GSK RSV vaccine for use in adults aged 50 –
59 years “at increased risk for RSV disease” ( regulatory decision expected
June 2024 )
3.Consideration of whether shared clinical decision -making remains the
preferred policy option.35
36The Work Group notes that safety and efficacy were demonstrated in their phase 3
safety & efficacy trial, most notably:
oInterim efficacy analysis with median 9 months follow -up per participant
VE against RSV LRTI with ≥2 symptoms: 63.3% (95% CI 48.7 –73.7%)
VE against RSV LRTI with ≥3 symptoms: 63.0% (95% CI 37.3 –78.2%)
Two recorded RSV -associated hospitalizations, both in the placebo arm. Unable to estimate efficacy against
hospitalization.
No recorded RSV -associated deaths, including in the placebo arm.
oNo reported cases of GBS, ADEM, or other inflammatory neurologic events in clinical trials of mRNA -1345 (N=18,245
vaccine recipients in their pivotal Phase II/III trial).
oNo reported cases of confirmed myocarditis or pericarditis among recipients of mRNA -1345 within 42 days after
vaccination.
If licensed by FDA for use in adults 60 and older, Work Group plans to present full GRADE/ EtR to support ACIP deliberations around adding Moderna mRNA -1345 as an
option for adults 60 and older to protect against lower respiratory tract disease. Work Group interpretations of initial phase 3 safety and
efficacy of Moderna’s mRNA -1345 RSV vaccine
Abbreviations: VE = Vaccine effectiveness, LRTI=Lower respiratory tract infection, GBS=Guillain -Barré Syndrome, ADEM=Acute disse minated
encephalomyelitis
37In October 2023, GSK presented data to ACIP demonstrating that the humoral immune
response to a single dose of GSK RSV vaccine in adults 50 –59 years is non -inferior to that in
adults 60 and older .
The Work Group noted that if FDA licensure is granted for use of GSK’s RSV vaccine in adults aged 50– 59 years at increased risk of RSV disease, then ACIP will likely need to make a policy
recommendation on:
–Whether RSV vaccination should be recommended in this age group?
–And if so, how will CDC define populations at increased risk of RSV disease?
Today we saw data demonstrating the relative risk of severe RSV disease across a range of chronic medical conditions by age group.
Work Group members broadly agree that use of RSV vaccine among adults with certain chronic medical conditions aged 50 –59 years is likely to have public health benefit, however,
upcoming data on safety and effectiveness will be pivotal to determine the preferred policy option in this age group. Work Group interpretations of GSK RSV vaccine for use in
adults 50 –59 at increased risk of RSV disease
38Lastly, the Work Group has begun analyzing the experience with shared clinical
decision -making this season.
Feedback from many partners that shared clinical decision- making has been
challenging to implement.
For the time being, the Work Group continues to endorse shared clinical decision-making as we learn more about the estimated benefits and potential risks associated with the currently available RSV vaccines.
However, the Work Group has begun reviewing evidence to discuss changing the current recommendation for adults ≥60 from shared clinical decision- making to:
–A universal  recommendation among adults older than a specific age cut -off AND
–A risk-based  recommendation in adults 50 years and older up to that age cut -off Work Group interpretations on whether shared clinical
decision -making will remain the preferred policy option
39The Work Group is considering a shift away from shared
clinical decision -making for multiple reasons.
A universal recommendation among adults over a specific age cut -off may be easier
to message and implement.
A risk -based recommendation among adults 50 and older, but below the universal
age cut -off may be easier to implement (persons at risk would be more concretely
defined) and ensure persons being vaccinated have highest potential to benefit.
Anticipate presenting additional data on these topics at the June 2024 ACIP meeting
The Work Group emphasizes that future preferred policy options will be contingent
on incoming data, including safety analyses and vaccine effectiveness.
40CDC and the Adult RSV Work
Group will continue to
transparently share new
information with ACIP and
the public and incorporate it
into future policy
recommendations to ensure
the greatest benefit and least
risk in the RSV vaccine
program for older adults. The first -ever respiratory virus season in which there were vaccines available to protect
older adults against RSV disease is coming to a close .
This is a new vaccine program and remains an evolving landscape with the potential for
new products and expansion of current products into new age groups.
Data from this season is still incoming. Over the coming months CDC and the Work Group will be analyzing these data to inform discussion of future RSV vaccine policy for
older adults.
Data from pre -licensure clinical trials and early findings from post- licensure vaccine
safety surveillance suggests the potential for increased risk of GBS after RSV vaccination in older adults; however, these early data are insufficient to confirm if there is an
increased risk.
Assessing the risk for GBS following receipt of the RSV vaccine among older adults in more robust analyses in active vaccine safety surveillance systems will be crucial and is
underway.
Currently, the Work Group continues to endorse the benefits of RSV vaccination for
adults 60 and older, especially those at increased risk of severe RSV disease, using shared
clinical decision -making.
Benefits can be maximized by administering RSV vaccine just before the start of RSV
season and the Work Group recommends that timing of RSV vaccination should be a part of the shared clinical decision -making discussion. Summary
For more information, contact CDC
1-800- CDC- INFO (232 -4636)
TTY:  1 -888 -232-6348    www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official
position of the Centers for Disease Control and Prevention.
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.

Summary: Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. RSV Vaccination in Older Adults: Work Group Interpretations Amadea Britton, MD Advisory Committee on Immunization PracticesFebruary 29, 2024 2This includes follow- up of…


01 Meningitis Loehr 508

Introduction to Meningococcal Vaccines Session
Jamie Loehr, MD
ACIP Meningococcal Work Group Chair
February 29, 2024National Center for Immunization & Respiratory Diseases
The findings and conclusions in this presentation are those of the authors and do not necessarily represent the official
position of the Centers for Disease Control and Prevention.
▪Revisiting the adolescent meningococcal vaccine
schedule
–Does ACIP concur with the 4 options for further assessment?
–What additional information will help ACIP determine the preferred
option?
▪GSK’s MenABCWY  vaccineTwo Terms of Reference
2 of 6
Upcoming ACIP Meetings
▪February 2024
•Terms of reference
–Adolescent schedule change
–GSK’s MenABCWY  vaccine
▪June 2024
•U.S. epidemiology
–Disease burden stratified by race/ethnicity in adolescents
–Cases/deaths averted by MenACWY  dose at 11 -12 years
–Risk factors for serogroup B disease among college students
–Breakthrough disease in vaccinated individuals
•WG considerations
3 of 6
Upcoming ACIP Meetings, cont.
▪October 2024
•GRADE/ EtR
•Cost -effectiveness analysis
▪February 2025
•Vote
4 of 6
Evidence to be Reviewed by the Work Group
▪Epidemiology of meningococcal disease
▪Expected public health impact
▪Immunogenicity and safety*
▪GRADE and EtR
▪Cost -effectiveness
*GSK Pentavalent vaccine only5 of 6
Meningococcal Vaccines Work Group Members
ACIP Members on the WG
•Jamie Loehr (Chair)
•Wilbur Chen
Ex Officio WG Members
•Margaret Bash (FDA)
•Mark Connelly (FDA)
•Francisco Leyva (NIH)
WG Liaisons and Consultants
•Katherine Poehling (Wake Forest)
•Lynn Bahta (MN DOH)
•Amra Resic  (AAFP)
•Samir Shah (AAP)
•Barbara Fluty (ACHA)
•Karyn Lyons (AIM)
•Paul Cieslak (CSTE)
•Kathy Hsu (IDSA)
•Joseline Zafack (NACI)
•Jeff Goad (NFID)
•Jessica Cataldi (PIDS)
•Amy Middleman (SAHM)
•David Stephens (Emory) CDC Contributors
•Sarah Schillie (DBD/NCIRD)
•Jennifer Collins (DBD/NCIRD)
•Lucy McNamara (DBD/NCIRD)
•Xiaoyu Dong (ISD/NCIRD)
•Ismael Ortega -Sanchez (CORVD/NCIRD)
•Andrew Leidner (ISD/NCIRD)
•LeAnne Fox (DBD/NCIRD)
•Susan Hariri (DBD/NCIRD)
•Amy Rubis (DBD/NCIRD)
•Noele Nelson (DBD/NCIRD)
•Alison Albert (DBD/NCIRD)
•Angela Jiles (DBD/NCIRD)
•Jonathan Duffy (DHQP/NCEZID)
•Tanya Myers (DHQP/NCEZID)
•Liz Velazquez (ISD/NCIRD)
•Jessica MacNeil (ACIP Secretariat)
•Melinda Wharton (ACIP Secretariat)
GRADE/ EtR Support
•Doug Campos -Outcalt (Arizona)
•Rebecca Morgan (Case Western Reserve)6 of 6

Summary: Introduction to Meningococcal Vaccines Session Jamie Loehr, MD ACIP Meningococcal Work Group Chair February 29, 2024National Center for Immunization & Respiratory Diseases The findings and conclusions in this presentation are those of the authors and do not necessarily represent the official  position of the Centers for Disease Control and Prevention. ▪Revisiting the adolescent meningococcal vaccine  schedule –Does ACIP concur with the 4 options for further assessment? –What additional…


02 Meningitis Schillie 508

Revising the Adolescent Meningococcal Vaccine Schedule:
Term of Reference and Considerations
Sarah Schillie, MD, MPH, MBA
February 29, 2024National Center for Immunization & Respiratory Diseases
The findings and conclusions in this presentation are those of the authors and do not necessarily represent the official
position of the Centers for Disease Control and Prevention.
▪Vaccine recommendations and coverage
▪Epidemiology
▪Duration of vaccine -induced protection
▪Options for changing the immunization scheduleOutline
2 of 24
*Both (all) doses must be from same manufacturerAdolescent Meningococcal Vaccine Recommendations
▪MenACWY :
•Dose #1:  11 –12 years
•Dose #2:  16 years
▪MenB * (shared clinical decision -making)
•2- or 3-dose series between 16 –23 years of age (preferred range:  16 –18 years)
▪MenABCWY :
•Recommended when both MenACWY  and MenB  indicated at same visit
3 of 24
▪MenACWY
–≥1 dose at 13 years:  84.5% (81.3% -87.2%)*
–≥1 dose at 16 years:  89.8% (87.4% -91.8%)
–≥2 doses at 17 years:  60.8% (57.5% -63.9%)**
▪MenB
–≥1 dose at 17 years:  29.4% (26.5% -32.4%)
–≥2 doses at 17 years:  11.9% (10.0% -14.1%)2022 Meningococcal Vaccine Coverage
*Coverage varies by metropolitan statistical area, poverty status, race/ethnicity, and health insurance status, although conf idence
intervals largely overlap
**Does not include adolescents who received 1st dose of MenACWY  vaccine at age ≥16 years
Pingali C, et al. MMWR Morb  Mortal Wkly  Rep 2023:  http://dx.doi.org/10.15585/mmwr.mm7234a34 of 24
Meningococcal Disease Incidence ― United States, 1996 -2022*
x
5 of 24
*2021 -2022 NNDSS data are preliminary
Average Annual Meningococcal Disease Incidence by
Age-Group and Serogroup ― United States, 2020 -2022*
6 of 24
Average Annual Meningococcal Disease Incidence by
Age-Group and Serogroup ― United States, 2012 -2021*
7 of 24
▪Preliminary data indicate 416* cases in 2023
–Highest number of cases since 2014
▪Rates of disease greatest in children <1 year of age
▪Second peak in adolescence; among cases in 2021:
–19 of 210 (9.0%) total cases in 11 -23 year -oldsIncreasing Case Counts
*Confirmed and probable cases8 of 24
▪Among adolescents 11 -15 years old, incidence decreased:
–16.3% (12.1% -20.3%) during prevaccine  period
–27.8% (20.6% -34.4%) during post -primary dose period
▪Among adolescents 16 -22 years old, incidence decreased:
–10.6% (6.8% -14.3%) during post -primary dose period
–35.6% (29.3% -41.0%) during post -booster dose period
▪Estimated 222 cases of serogroup C,W,Y disease averted
through vaccination of adolescents from 2006 -2017Cases Averted Due to Vaccination
Mbaeyi S, et al. JAMA Pediatr  2020  9 of 24
Incidence of Meningococcal Disease by Serogroups Following
MenACWY  Vaccine Implementation
Source: National Notifiable Diseases Surveillance System (NNDSS) data with additional serogroup data from Active Bacterial Co re surveillance (ABCs) and state health departments ACWY disease incidence substantially
decreased  in adolescentsB disease incidence was similar  in
adolescents over time
00.050.10.150.20.250.3
11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26Incidence per 100,000
AgeSerogroups A, C, W, Y
2006-2010 2015-201900.050.10.150.20.25
11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26Incidence per 100,000
AgeSerogroup B
2006-2010 2015-2019 10 of 24
▪College students have a 3.5 -fold (95% CI: 2.2 -5.4) higher risk of serogroup B
disease than non -college students
▪Serogroup B incidence peaks for 19 year -old college students and declines
after age 20
Serogroup B Disease Risk is Higher among
College Students
Mbaeyi S, et al.  Pediatr  2019  11 of 24
Additional Factors Associated with
Increased Risk among College Students
▪4-year college students had a 5.2-fold (95% CI: 3.6 -7.7) higher risk of serogroup B
disease than non -undergraduates aged 18 -24 years
–Risk among 2 -year college students was comparable to non -undergraduates (RR 1.0,
95% CI: 0.4 -2.1)
▪First -year students were at 3.8-fold (95% CI: 2.4 -6.0) higher risk of serogroup B
disease than non -first-year students
▪On-campus residents at  2.9-fold (95% CI: 1.8 -4.6) higher risk of serogroup B
disease than off -campus residents
▪Students participating in Greek life were at 9.8-fold (95% CI: 4.6 -21.2) higher risk
of serogroup B disease than other students during outbreaks
Weil L, et al. OFID 2023  12 of 24
▪MenACWY
–Protection wanes 3 to <8 years postvaccination
•<1 year:  79%
•1 to <3 years:  69%
•3 to <8 years:  61%
▪MenB
–Protection wanes 1 -2 years following primary vaccinationDuration of Vaccine -Induced Protection
Mbaeyi S, et al. MMWR Recomm  Rep 2020  https://www.cdc.gov/mmwr/volumes/69/rr/pdfs/rr6909a1 -H.pdf ; Stephens D, et al.
in Plotkin’s Vaccines 8th edit 2024; Dretler  A, et al. Hum Vacc & Immuno  2018; Cohn A, et al. Pediatr  2018
13 of 24
▪Bexsero is recommended for prevention of serogroup B
meningococcal disease
–Some protection against gonorrhea is also likely
▪N. meningitidis and N. gonorrhoeae closely genetically
related
– ~80 to 90% sequence homology
▪Potential for outer membrane vesicle (OMV) -containing
MenB  vaccines (e.g., Bexsero) to provide protection against
N. gonorrhoeae
Petousis -Harris H, et al. Lancet 2017;  Wang B, et al. Lancet 2022; Abara W, et al. Lancet 2022;  Bruxvoort  K, et al. CID 2023Effectiveness of Bexsero against Gonorrhea
14 of 24
▪Revisions to the schedule should optimize protection
against meningitis
▪Considerations for meningitis protection include:
–Ages at higher risk for meningitis
–Recent meningitis epidemiology
–Duration of vaccine -induced protection
15 of 24Revising the
Adolescent Meningococcal Vaccine Schedule
▪Maintaining harmonization with existing adolescent
vaccination platform
▪Pentavalent vaccine provides opportunity to reduce
number of injections
16 of 24Revising the
Adolescent Meningococcal Vaccine Schedule, cont.
▪MenACWY
–Possibly eliminate 11 -12 year -old dose
–Change recommended age given recent epidemiology
▪MenB
–Change recommended age to increase protection upon college entry
–Routine or risk -based recommendation
•If risk -based recommendation, include permissive language for vaccination of persons
in age group requesting protection but who may lack risk factors such as college
attendance (equity considerations)  Options for Revising
Adolescent Meningococcal Vaccine Schedule
17 of 24
Schedule Options for Further Consideration
OptionACWY
Dose#1ACWY
Dose#2B Dose#1 B Dose#2
Current
recomm .11–12 yrs 16 yrs16 yrs – 23 years (preferred 16 –18 yrs)
SCDM
1 11–12 yrs 16 yrs 16 yrs 17–18 yrs
2 11–12 yrs 16 yrs 16 yrs risk-based 17–18 yrs risk-based
3 No dose 16 yrs 16 yrs risk -based 17–18 yrs risk-based
4 15 yrs 17–18 yrs 17–18 yrs 17–18 yrs
Proposed recommendations are for routine vaccination unless specified as
“risk -based”; option numbers do not represent ordering of preference
SCDM, shared clinical decision -making 18 of 24
Schedule Options for Further Consideration, etc.
OptionACWY
Dose#1ACWY
Dose#2B Dose#1 B Dose#2
Current
recomm .11–12 yrs 16 yrs16 yrs – 23 years (preferred 16 –18 yrs)
SCDM
1 11–12 yrs 16 yrs 16 yrs 17–18 yrs
2 11–12 yrs 16 yrs 16 yrs risk-based 17–18 yrs risk-based
3 No dose 16 yrs 16 yrs risk -based 17–18 yrs risk-based
4 15 yrs 17–18 yrs 17–18 yrs 17–18 yrs
Proposed recommendations are for routine vaccination unless specified as
“risk -based”; option numbers do not represent ordering of preference
SCDM, shared clinical decision -making 19 of 24
Schedule Options for Further Consideration, etc.
OptionACWY
Dose#1ACWY
Dose#2B Dose#1 B Dose#2
Current
recomm .11–12 yrs 16 yrs16 yrs – 23 years (preferred 16 –18 yrs)
SCDM
1 11–12 yrs 16 yrs 16 yrs 17–18 yrs
2 11–12 yrs 16 yrs 16 yrs risk-based 17–18 yrs risk-based
3 No dose 16 yrs 16 yrs risk -based 17–18 yrs risk-based
4 15 yrs 17–18 yrs 17–18 yrs 17–18 yrs
Proposed recommendations are for routine vaccination unless specified as
“risk -based”; option numbers do not represent ordering of preference
SCDM, shared clinical decision -making20 of 24
▪Variability in desire to keep vs. eliminate 11 –12 year -old dose of
MenACWY
–Favor keeping:  Has taken years to ingrain the 11 –12 year -old platform, 11 –12
year -old dose may have reduced carriage and ‘worked’
–Favor eliminating:  Epi seems to support starting series at 16 years
▪Consider administering MenB  dose #1 at age 15 years*
▪Try to achieve acceptable efficacy for duration of disease incidence peak in
young adulthoodSynthesis of Work Group Comments
*Not among 4 options for consideration 21 of 24
▪Oppose SCDM recommendations
–Poor uptake, missed opportunities, implementation challenges, lack of strong
recommendation prevents many institutions from implementing policies, not
understandable to clinicians
–Interest in changing MenB  to risk -based or routine recommendation
▪Harmonization of MenACWY  and MenB  schedules may reduce number of
injections
–Extra antigen administration (as may occur with administration of pentavalent
vaccine) has not been a concern before
▪Change in schedule may impact school requirements Synthesis of Work Group Comments, cont.
22 of 24
▪Does ACIP concur with the 4 schedule
options for further assessment?
▪What additional information will help ACIP
determine the preferred option?Discussion
23 of 24
Acknowledgements
▪Lucy McNamara
▪Jennifer Collins
▪Samuel Crowe
▪Sancta St. Cyr
24 of 24

Summary: Revising the Adolescent Meningococcal Vaccine Schedule:   Term of Reference and Considerations  Sarah Schillie, MD, MPH, MBA February 29, 2024National Center for Immunization & Respiratory Diseases The findings and conclusions in this presentation are those of the authors and do not necessarily represent the official  position of the Centers for Disease Control and Prevention. ▪Vaccine recommendations and coverage ▪Epidemiology ▪Duration of vaccine -induced protection ▪Options for changing the…


03 Meningitis Schillie 508

GSK Pentavalent MenABCWY  Vaccine:  Term of Reference
Sarah Schillie, MD, MPH, MBA
February 29, 2024National Center for Immunization & Respiratory Diseases
The findings and conclusions in this presentation are those of the authors and do not necessarily represent the official
position of the Centers for Disease Control and Prevention.
▪Two new MenABCWY  vaccines:
–Pfizer (“ Penbraya ,” ACIP voted October 2023)
–GSK (clinical trials)
▪Each vaccine is a combination of an existing:
–MenACWY  vaccine   and
–MenB  vaccine
▪Each vaccine assessed separately by Work Group
–Lack of data directly comparing Pfizer and GSK Pentavalent vaccinesPentavalent MenABCWY  Vaccines
2 of 10
Pfizer ( Penbraya ) GSK*
ACWY
componentNimenrix  (not licensed in U.S.) Menveo
B component Trumenba Bexsero
Schedule 2 doses, 6 months apart 2 doses, 6 months apart*
Age 10-25 years 10-25 years*
Clinical trial
participantsStudied in MenACWY  primed
and naive subjects; all MenB
naiveStudied in MenACWY  primed
and naive subjects; MenB
naïve in phase 3 trials
Future studiesLonger interval studies
underwayLonger interval studies
underway
Gonorrhea
protectionNo Yes/some
*Vaccine not yet licensed in U.S. and this slide represents anticipated schedule and age indications Pfizer’s and GSK’s MenABCWY  Vaccines
3 of 10
Policy Questions for GSK’s Pentavalent Vaccine
▪Should the pentavalent vaccine be included as an option for MenACWY /MenB
vaccination in people currently recommended to receive both vaccines at the
same visit?
– For example, 16 year olds*
▪Should the pentavalent vaccine be included as an option for people currently
recommended to receive MenACWY  only?
–For example, 11 –12 year olds
▪Should the pentavalent vaccine be included as an option for people currently
recommended to receive MenB  only?
– For example, during a serogroup B outbreak
*16 year olds who decide to receive the MenB  vaccine based on shared clinical decision making4 of 10
Outcomes Table
Outcome Importance* To be Included in Evidence Profile
Meningococcal disease caused by
serogroups A, B, C, W, and YCritical Yes
Persistent immunity Important Yes
Short -term immunity Critical Yes
Interference with other
recommended vaccines
administered concurrentlyImportant Yes
Serious adverse events Critical Yes
Non -serious adverse events Important Yes
Gonorrhea prevention Important Yes
* Three options: critical, important but not critical, of limited importance for decision making. 5 of 10
PICO policy question #1 (of 3) — Should the GSK pentavalent vaccine be included as an
option for MenACWY/ MenB  vaccination in people currently recommended to receive
both vaccines at the same visit?
Population All individuals aged 10 years or older currently recommended to receive
MenACWY and MenB  vaccines at the same visit
Intervention Vaccination with GSK’s pentavalent vaccine
Comparison Vaccination with a currently licensed MenACWY vaccine and a MenB vaccine
Outcomes •Meningococcal disease caused by serogroups A, B, C, W, and Y
•Short -term immunity
•Persistent immunity
•Interference with other recommended vaccines administered concurrently
•Serious adverse events
•Non -serious adverse events
•Gonorrhea prevention6 of 10
PICO policy question #2 (of 3) — Should the GSK pentavalent vaccine be included
as an option for people currently recommended to receive  MenACWY only ?
Population All individuals aged 10 years or older currently recommended to receive
MenACWY  vaccine only
Intervention Vaccination with GSK’s pentavalent vaccine
Comparison Vaccination with a currently licensed MenACWY vaccine
Outcomes •Meningococcal disease caused by serogroups A, C, W, and Y
•Short -term immunity
•Persistent immunity
•Interference with other recommended vaccines administered concurrently
•Serious adverse events
•Non -serious adverse events
•Gonorrhea prevention 7 of 10
PICO policy question #3 (of 3) — Should the GSK pentavalent vaccine be included
as an option for people currently recommended to receive MenB only ?
Population All individuals aged 10 years or older currently recommended to receive MenB
vaccine only
Intervention Vaccination with GSK’s pentavalent vaccine
Comparison Vaccination with a currently licensed MenB  vaccine
Outcomes •Meningococcal disease caused by serogroup B
•Short -term immunity
•Persistent immunity
•Interference with other recommended vaccines administered concurrently
•Serious adverse events
•Non -serious adverse events
•Gonorrhea prevention 8 of 10
Discussion
9 of 10
Acknowledgements
▪Lucy McNamara
▪Jennifer Collins
▪Samuel Crowe
▪Sancta St. Cyr▪CDC Division of STD
Prevention
10 of 10

Summary: GSK Pentavalent MenABCWY  Vaccine:  Term of Reference   Sarah Schillie, MD, MPH, MBA February 29, 2024National Center for Immunization & Respiratory Diseases The findings and conclusions in this presentation are those of the authors and do not necessarily represent the official  position of the Centers for Disease Control and Prevention. ▪Two new MenABCWY  vaccines: –Pfizer (“ Penbraya ,” ACIP voted October 2023) –GSK (clinical trials) ▪Each vaccine is a combination of an existing: –MenACWY …


01 Pneumococcal Loehr 508

Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.
Pneumococcal Vaccines
February 2024, ACIP Meeting
February 29, 2024
Pneumococcal Vaccine Work Group ChairJames Loehr, MD, FAAFP
ACIP Members
Jamie Loehr  (Chair, acting)
Sarah Long
Ex Officio Members
Jeffrey Kelman  (CMS)
Lucia Lee            (FDA)
Tina Mongeau   (FDA)
Uzo  Chukwuma (IHS)
Mamodikoe Makhene (NIH, primary)
Meenu Upadhyay (NIH, alternate)
Liaison Representatives
Lynn Fisher                (AAFP)
James Campbell      (AAP/COID)
Jason Goldman         (ACP)
David Nace                 (AGS/ AMDA)
Cora Hoover               (AIM, primary)Risa Claytor                 (HRSA)
James McAuley         (IDSA)
Eva Wong                 (NACI)
Robert Hopkins    (NFID, primary)
William Schaffner     (NFID, alternate)
Virginia Caine            (NMA)
Consultants
Monica Farley            (VAMC/Emory)
Keith Klugman          (BMGF)
Kathy Poehling         (Wake Forest)
Arthur Reingold        (UC Berkley)
Lorry Rubin                 (CCMC)
Richard Zimmerman (U. of Pittsburgh)Pneumococcal Vaccines Work Group
Division of Bacterial Diseases
Diepreye Ayabina
Adam Cohen
Ryan Gierke
Jennifer Farrar
Noele Nelson
Immunization Safety Office
Pedro Moro
Immunization Services Division
Janelle King
Andrew Leidner
Liz VelazquezArctic Investigations Program
Marc Fischer
CDC Lead
Miwako Kobayashi
GRADE/ EtR  consultants
Doug Campos -Outcalt
Rebecca MorganCDC Contributors and Consultants
Invasive pneumococcal disease incidence reached a historically low level
early in the COVID -19 pandemic but is returning toward pre -COVID
levels
IPD=invasive pneumococcal disease; 2022 data in gray are preliminary
ABCs Bact  Facts Interactive Data Dashboard | CDC

Around the same time, pneumococcal conjugate vaccines PCV15
and PCV20  were recommended for both adults and children
2021 2023 2022
PCV15:  ChildrenPCV20:  Expanded
indication for adults
who previously received PCV13
PCV20:  ChildrenPCV15 and PCV20:
Adults who have not received PCV or whose vaccination history is unknown
Additional Pneumococcal Vaccines in Advanced Stages of Development
1 3 4 5 6
A6B7 F9V1418C19A19F23F22F33F8 1
0
A11
A1
2F15B2 9N17F2015A15C16F23A23B24F3135B
PCV15
PCV20PPSV23
Pn-
MAPS24v20
B
VAX -2420B
V11620
A
1. Chichili  et al. Vaccine 2022; GSK Pipeline assets and clinical trials appendix Q4 2023  2. Wassil et al. Lancet ID 2023, ClinicalTrials.gov ID: NCT05297578, and NCT05844423; 3. FDA Grants Priority Review to Merck’s
New Biologics License Application for V116, an Investigational, 21- valent Pneumococcal Conjugate Vaccine Specifically Designed t o Protect Adults -  Merck.com . 24-valent pneumococcal vaccines:
•Pn-MAPS24v (GSK): Completed phase 1/2 study for adults; Breakthrough  Therapy Designation
granted and Phase 3 study in preparation; undergoing phase 2 studies in infants1
•VAX -24 (Vaxcyte ): Completed phase 1/2 studies for adults, undergoing phase 2 studies in infants2
21-valent pneumococcal conjugate vaccine (V116, Merck):
• BLA accepted by the FDA for priority review3
25-valent  pneumococcal vaccine candidate (IVT PCV -25, Iventprise )
•Completed Phase 2 dose ranging  study in young adults1
31-valent  pneumococcal conjugate vaccine candidate (VAX- 31, Vaxcyte )
•Completed enrollment of Phase 1/2 study in adults aged ≥50 years2Additional Pneumococcal Vaccines Under Development
1. Inventprise  Completes Vaccination of Participants in a Phase 2 Dose Ranging Study of its 25 Valent Pneumococcal Vaccine Candidate –  Inventprise
2. Vaxcyte  Completes Enrollment of Phase 1/2 Study Evaluating VAX- 31 for the Prevention of Invasive Pneumococcal Disease (IPD) in Adults Aged 50 and Older - Vaxcyte , Inc.
The following groups are currently recommended to receive a dose of
pneumococcal conjugate vaccine (PCV):
•Adults aged ≥65 years who have not received a PCV1
•Adults aged 19 –64 years with certain underlying conditions or risk factors2 who have
not received a PCV1
•Certain adults who have received PCV13 but have not received PCV203 Current Pneumococcal Vaccine Recommendations for Adults
and Vaccine Coverage
1. Excludes PCV7
2. alcoholism; chronic heart, liver, or lung disease; chronic renal failure; cigarette smoking; cochlear implant; congenital or acquired asplenia; CSF leak; diabetes mellitus; generalized malignancy; HIV infection;
Hodgkin disease; immunodeficiency; iatrogenic immunosuppression; leukemia, lymphoma, or multiple myeloma; nephrotic syndrome;  solid organ transplant; or sickle cell disease or other
hemoglobinopathies
3. Adults who have not completed the recommended vaccine series, or shared clinical decision -making for adults aged ≥65 years who h ave completed the recommended vaccine series
Pneumococcal Vaccine for Adults Aged ≥19 Years: Recommendations of the Advisory Committee on Immunization Practices, United S tates, 2023 | MMWR (cdc.gov)
Coverage of ≥1 dose of any pneumococcal vaccine
•Adults aged 19 –64 years with risk- based indication: 22.2%
•Adults aged ≥65 years: 65.8%Adults with risk -based vaccine recommendations have lower
vaccine coverage compared with those with age -based
recommendations
Vaccination Coverage among Adults in the United States, National Health Interview Survey, 2021 | CDC
1. Should PCV21 be recommended for U.S. adults aged ≥19 years who
currently have a recommendation to receive a PCV*?
*Includes,
• Adults aged ≥65 years who have never received a PCV
• U.S. adults aged 19– 64 years with a risk condition, who have never received a PCV
• U.S. adults aged ≥19 year who have received a PCV (i.e., PCV7, PCV13, or PCV15), but have not completed the recommended series
2. Should PCV21 be recommended for U.S. adults aged 50 –64 years who
currently do not have a risk -based pneumococcal vaccine indication?
3. Should PCV21 be recommended for U.S. adults aged 19– 49 years who
currently do not have a risk -based pneumococcal vaccine indication?
•Questions 2 and 3 would result in a new age -based recommendation for these groups.Policy Questions Being Considered by the Work Group
Considering:
Additional pneumococcal vaccines for adults are currently under investigation and
may be approved in the near future, and
Dynamic changes in pneumococcal disease incidence are anticipated post -COVID -19
and with increased uptake in PCV15/PCV20 in children and adults

1. Do you have any feedback on the policy questions being considered by the WG?2. What additional data would be helpful to inform the discussions on PCV21 use in
adults? Questions for the Committee
Introduction Dr. Jamie Loehr (ACIP , WG Chair)
Current epidemiology of invasive pneumococcal
disease among adults in the United StatesMr. Ryan Gierke (CDC, NCIRD)
Interim results from the Pneumococcal pNeumonia  Epidemiology, Urine serotyping, and
Mental Outcomes (PNEUMO) US studyDr. Wesley Self (Vanderbilt University Medical Center)
Phase 3 clinical trial data of PCV21 Dr. Heather Platt
Post -licensure PCV20 safety dataDr. Pedro Moro (CDC/NCEZID)Dr. Richard Forshee  (FDA)
Preliminary WG interpretations of EtR and Next
StepsDr. Miwako Kobayashi (CDC, NCIRD)Today’s Session

Summary: Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Pneumococcal Vaccines February 2024, ACIP Meeting February 29, 2024 Pneumococcal Vaccine Work Group ChairJames Loehr, MD, FAAFP ACIP Members Jamie Loehr  (Chair, acting)…