11 RSV Adult Melgar Roper Britton 508

1
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.
Evidence to Recommendations Framework (EtR):
RSV Vaccination in Adults Aged 50 –59 years, 60 –74 years,
and 75 years and older
Amadea Britton, MD, Co -Lead Adult RSV Vaccine Work Group
Michael Melgar, MD, Co -Lead Adult RSV Vaccine Work Group
Lauren Roper, MPH
Coronavirus and Other Respiratory Viruses Division (CORVD)
Advisory Committee on Immunization Practices (ACIP)
June 26, 2024
2▪Should alladults aged ≥75 years be recommended to receive a single dose
of RSV vaccination?
▪Should adults aged 60–74years at increased risk of severe RSV disease be
recommended to receive a single dose of RSV vaccination?
▪Should adults aged 50–59years at increased risk of severe RSV disease be
recommended to receive a single dose of RSV vaccination?Policy questions
3We will consider the first two questions together in EtR and
then return to the 50 –59 age group.
4Evidence to Recommendations ( EtR ) framework
ACIP Evidence to Recommendations Framework (cdc.gov)EtR Domain Question(s)
Public Health Problem ▪Is the problem of public health importance?
Benefits and Harms ▪How substantial are the desirable anticipated effects?
▪How substantial are the undesirable anticipated effects?
▪Do the desirable effects outweigh the undesirable effects?
Values ▪Does the target population feel the desirable effects are large relative
to the undesirable effects?
▪Is there important uncertainty about, or variability in, how much
people value the main outcomes?
Acceptability ▪Is the intervention acceptable to key stakeholders?
Feasibility ▪Is the intervention feasible to implement?
Resource Use ▪Is the intervention a reasonable and efficient allocation of resources?
Equity ▪What would be the impact of the intervention on health equity?
5
EtR Domain: Public Health Problem
Is the problem of public health importance among adults aged ≥75 years?
Is the problem of public health importance among adults aged 60 –74
years at increased risk of severe RSV disease?
6RSV was associated with1
90,000 –140,000 annual
hospitalizations in
U.S. adults aged 65 years and older
and
10,000 –20,000 annual
hospitalizations in
U.S. adults aged 60–64 yearsInfluenza* was associated with2
170,000 –470,000 annual
hospitalizations in
U.S. adults aged 65 years and olderDuring 2016 –2020, CDC estimates:
1. Preliminary CDC RSV -NET data 2016 –2020 (unpublished). Updated from prior CDC estimates
which are available at: https://www.cdc.gov/rsv/php/surveillance/index.html
Ranges reflect point estimates for individual seasons, but not uncertainty in those estimates2. CDC Influenza Burden 2016 –2020: https://www.cdc.gov/flu/about/burden/past -seasons.html  *Annual influenza disease burden is attenuated
by the routine vaccination program.
70200400600800
18–49 50–54 55–59 60–64 65–69 70–74 75–79 ≥80 Annual RSV -associated hospitalizations
per 100,000 population
Age group, years2016 –17
2017 –18
2018 –19
2019 –20
Unpublished data. Rates are adjusted using multipliers for the frequency of RSV testing during each season and the sensitivit y of RSV diagnostic tests. Error bars represent 95%
confidence intervals.
*Estimated rates exclude recorded hospitalizations among pregnant adults.
https://www.cdc.gov/rsv/research/rsv -net/index.html  Estimated annual RSV -associated hospitalization  rates per 100,000 adults*
≥18 years by age group and year, RSV -NET, 2016 –17 to 2019 –20
Surveillance
season:
8Adjusted Rate Ratios for RSV -Associated Hospitalization by Chronic
Condition among Community -Dwelling Adults Aged ≥50 Years
6.5
4.63.7
3.12.4
2.0 1.91.5 1.3
0.11.010.0100.0
Chronic
Kidney
DiseaseCOPD Severe
obesity
(BMI ≥40)Asthma Coronary
Artery
DiseaseDiabetes
mellitusCurrent
smokerStroke Obesity
(BMI 30-39)aRR
Unpublished data. Update on analysis from Woodruff et al. First presented to ACIP in February 2024: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2024 -02-28-29/03 -RSV-Adults -Woodruff -508.pdf
BMI: Body Mass Index (kg/m2), COPD: Chronic Obstructive Pulmonary Disease, aRR: adjusted rate ratio. Data are preliminary and unpublished. Adjusted rate ratios and 95% confidence intervals are derived fr om Poisson
regression using Monte Carlo simulation methods and adjust for age, sex and race and ethnicity group. Error bars represent 95 % confidence intervals.
9aRR (95% CI)1
No. of chronic conditions2
0 ref
1 2.1 (1.4, 3.2)
≥2 7.3 (5.0, 10.6)
Age group, years
50–59 ref
60–74 1.9 (1.3, 2.7)
≥75 6.0 (4.2, 8.6)
Race or ethnicity group
White, non -Hispanic ref
Black, non -Hispanic 1.1 (0.8, 1.5)
Other race or Hispanic ethnicity 1.7 (1.3, 2.5)
Sex
Male Ref
Female 1.3 (1.0, 1.6)
1 Adjusted rate ratios ( aRR) and 95% confidence intervals (CI) were estimated using
Poisson regression using Monte Carlo simulation.
2 Includes history of asthma, chronic kidney disease, chronic obstructive pulmonary
disease, coronary artery disease, current smoker, diabetes, stroke, obesity (BMI 30 –39)
or severe obesity (BMI ≥40)Among community -dwelling
adults aged ≥50 years, a
history of ≥2 chronic
conditions  and age ≥75
years were the strongest
independent  risk factors for
RSV-associated
hospitalization.
Unpublished data. Update on analysis from Woodruff et al. First presented to ACIP in February 2024: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2024 -02-28-29/03 -RSV-Adults -Woodruff -508.pdf
10▪Other medical conditions associated with increased risk of severe RSV disease
–Heart failure
•As many as 28% of adults hospitalized with RSV infection have chronic heart failure1
•Among  adults 65 years and older, hospitalization rates are 3.5x higher in those with versus
without heart failure1
–Immune compromise
•Severe disease and high mortality (>20%), especially among lung transplant and
hematopoietic cell transplant recipients2,3
▪Persons living in long -term care facilities are also at increased risk of RSV hospitalization and
severe outcomes4,5
–Frequent cause of respiratory illness and outbreaks What do we know about conditions and risk factors not
included in the RSV -NET analysis?
1.Kujawski  SA, et al. (2022) Rates of respiratory syncytial virus (RSV) -associated hospitalization among adults with congestive heart fail ure—United States, 2015 –2017. PLOS ONE 17(3):
e0264890. https://doi.org/10.1371/journal.pone.0264890
2.Ison MG, Hirsch HH. Community -Acquired Respiratory Viruses in Transplant Patients: Diversity, Impact, Unmet Clinical Needs. Clin  Microbiol  Rev. 2019 Sep 11;32(4):e00042 -19.
https://pubmed.ncbi.nlm.nih.gov/31511250/
3.Manuel O, Estabrook M; American Society of Transplantation Infectious Diseases Community of Practice. RNA respiratory viral i nfections in solid organ transplant recipients: Guidelines
from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e1351 1 https://pubmed.ncbi.nlm.nih.gov/30817023/
4.Bosco E, et al. Estimated Cardiorespiratory Hospitalizations Attributable to Influenza and Respiratory Syncytial Virus Among Lon g-term Care Facility Residents. JAMA Netw  Open. 2021 Jun
1;4(6):e2111806. https://pubmed.ncbi.nlm.nih.gov/34106266/
5.Childs A, et al. The burden of respiratory infections among older adults in long -term care: a systematic review. BMC Geriatr . 2019 Aug 5;19(1):210 https://pubmed.ncbi.nlm.nih.gov/31382895/
11▪Among unvaccinated adults, disease severity of RSV -associated
hospitalization is similar to severity of COVID -19- and influenza -
associated hospitalization .1
▪High incidence of acute cardiac events among adults 50 and older
hospitalized with RSV infection, including 1 in 12 adults (8.5%) with no
documented underlying cardiovascular disease.2
▪Patients hospitalized for RSV -associated disease often require follow‐up
care and skilled nursing after discharge.3Other considerations: RSV disease severity and
complications among adults not vaccinated against RSV
1. Surie D, Yuengling KA, DeCuir J, et al. Severity of Respiratory Syncytial Virus vs COVID -19 and Influenza Among Hospitalized US Adults. JAMA Netw  Open. 2024 Apr 1;7(4):e244954. https://pubmed.ncbi.nlm.nih.gov/38573635/
2. Woodruff RC, Melgar M, Pham H, et al. Acute Cardiac Events in Hospitalized Older Adults With Respiratory Syncytial Virus Infecti on. JAMA Intern Med. 2024;184(6):602 –611. doi:10.1001/jamainternmed.2024.0212
3. Walsh E, Lee N, Sander I, Stolper  R, Zakar  J, Wyffels  V, Myers D, Fleischhackl  R. RSV -associated hospitalization in adults in the USA: A retrospective chart review investigating burden, management strategie s, and outcomes. Health
Sci Rep. 2022 Apr 14;5(3):e556. doi: 10.1002/hsr2.556. PMID: 35509398; PMCID: PMC9059216.
12▪Annual rate of RSV -associated hospitalization increases with increasing
age , with a steep rise at age 75 years.
▪Certain chronic medical conditions also increase risk of RSV -associated
disease. Age  and chronic medical conditions are independently  associated
with increased risk.
▪RSV is associated with severe disease and has significant post -
hospitalization sequelae among older adults.Public health problem: summary of the available evidence
Adults 60 years and older
13▪Is RSV of public health importance among adults aged  ≥75 years ?
▪Is RSV of public health importance among adults aged  60–74
years at increased risk of severe RSV disease ? Public Health Problem: Work Group interpretation
NoProbably
NoProbably
YesYes VariesDon’t
know
NoProbably
NoProbably
YesYes VariesDon’t
know
14
EtR  Domain: Benefits and Harms
- How substantial are the desirable anticipated effects?
- How substantial are the undesirable anticipated effects?
- Do the desirable effects outweigh the undesirable effects?
15▪Protein subunit RSV vaccines (Pfizer ABRYSVO, GSK AREXVY)
–Adults 75 years and older
•GRADE
•Additional considerations
–Adults aged 60 –74 years at increased risk of severe RSV disease
•GRADE
•Additional considerations
▪mRNA RSV vaccine (Moderna mRESVIA )
–Repeat as aboveBenefits and Harms overview
16GRADE Framework: PICO Question
Population Adults aged ≥75 years
Intervention Protein Subunit RSV Vaccine:
Pfizer ABRYSVO (1 dose IM) -or-GSK AREXVY (1 dose IM)
Comparison No RSV vaccine
Outcomes ▪RSV lower respiratory tract disease (LRTD)
▪Medically attended RSV LRTD
▪Hospitalization for RSV respiratory illness
▪Severe RSV respiratory illness requiring supplemental oxygen or
other respiratory support
▪Death due to RSV respiratory illness
▪Serious Adverse Events (SAEs)
▪Inflammatory neurologic events (e.g., Guillain -Barré syndrome)
▪Reactogenicity (grade ≥3)
17Summary of GRADE for protein subunit RSV vaccines in adults ≥75 years
Outcome ImportanceDesign
(# of studies)FindingsEvidence
type
Benefits
RSV Lower Respiratory Tract
Disease (LTRD)Important RCT (2)Protein subunit RSV vaccination reduces RSV LRTD in adults aged ≥75
years.High
Medically attended RSV LRTD Critical RCT (2)Protein subunit RSV vaccination likely reduces medically attended RSV
LRTD in adults aged ≥75 years.Moderate
Hospitalization for RSV
respiratory illnessCritical RCT (2)Protein subunit RSV vaccination may reduce hospitalization for RSV
respiratory illness in adults aged ≥75 years .Low
Severe RSV respiratory illness
requiring O2/respiratory
supportImportant RCT (2)Protein subunit RSV vaccination may reduce severe RSV respiratory
illness requiring supplemental oxygen or other respiratory support in
adults aged ≥75 years , but the effect is very uncertain.Very low
Death due to RSV respiratory
illnessImportant RCT (2) Zero events observed Unable to
evaluate
Harms
Serious adverse events (SAEs) Critical RCT (4)Protein subunit RSV vaccination likely results in little to no difference in
SAEs in adults aged ≥75 years.Moderate
Inflammatory neurologic events Critical RCT (4)Protein subunit RSV vaccination may increase inflammatory neurologic
events in adults aged ≥75 years, but the effect is very uncertain.Very low
Reactogenicity (grade ≥3) Important RCT (4)Protein subunit RSV vaccination may increase severe reactogenicity
events in adults aged ≥75 years.Low
18Summary of GRADE for protein subunit RSV vaccines in adults ≥75 years
Outcome ImportanceDesign
(# of studies)FindingsEvidence
type
Benefits
RSV Lower Respiratory Tract
Disease (LTRD)Important RCT (2)Protein subunit RSV vaccination reduces RSV LRTD in adults aged ≥75
years.High
Medically attended RSV LRTD Critical RCT (2)Protein subunit RSV vaccination likely reduces medically attended RSV
LRTD in adults aged ≥75 years.Moderate
Hospitalization for RSV
respiratory illnessCritical RCT (2)Protein subunit RSV vaccination may reduce hospitalization for RSV
respiratory illness in adults aged ≥75 years .Low
Severe RSV respiratory illness
requiring O2/respiratory
supportImportant RCT (2)Protein subunit RSV vaccination may reduce severe RSV respiratory
illness requiring supplemental oxygen or other respiratory support in
adults aged ≥75 years , but the effect is very uncertain.Very low
Death due to RSV respiratory
illnessImportant RCT (2) Zero events observed Unable to
evaluate
Harms
Serious adverse events (SAEs) Critical RCT (4)Protein subunit RSV vaccination likely results in little to no difference in
SAEs in adults aged ≥75 years.Moderate
Inflammatory neurologic events Critical RCT (4)Protein subunit RSV vaccination may increase inflammatory neurologic
events in adults aged ≥75 years, but the effect is very uncertain.Very low
Reactogenicity (grade ≥3) Important RCT (4)Protein subunit RSV vaccination may increase severe reactogenicity
events in adults aged ≥75 years.Low
19Additional information on benefits/harms for protein
subunit RSV vaccines in adults aged ≥75 years
20Per 1 Million Vaccine Doses Administered to Adults Aged ≥75 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. FDA self -controlled case series analysis, among CMS Medicare beneficiaries ≥65 years with Parts A, B, and D coverage who did not  have a GBS claim in the 365 days before vaccination. Analysis based on
diagnoses of GBS in inpatient claims data in risk interval (1 –42 days after RSV vaccination) compared to control interval (43 –90 days after RSV vaccination). GBS cases identified using ICD -10 diagnosis of
GBS in primary position of inpatient claims coding. Estimates adjusted for outcome -dependent observation time, positive predicti ve value of diagnostic codes in identifying chart -confirmed GBS cases, and
seasonality. Analysis includes patients with RSV vaccinations only through October 8, 2023 to allow for 90 -day post -vaccination observation and 90% or greater claims data completeness. Claims data
through April 6, 2024.
3. Self -controlled case series analysis estimated attributable risk of 3 (95% CI: -3, 10) GBS cases. However, the range was truncat ed at zero for Benefit/Risk analyses.Estimated RSV -Associated Outcomes1 Preventable over 2 RSV Seasons  vs. potential cases of GBS
(positive predictive value -adjusted  attributable risk of GBS in FDA -CMS partnership data among adults
aged ≥65 years, 42 -day risk interval2)
3 (range  0–10)3 attributable  cases of GBS 16 (range 3–29) attributable cases of GBS610 630 4,300
 -  1,000  2,000  3,000  4,000  5,000  6,000  7,000540 560 3,800
 -  1,000  2,000  3,000  4,000  5,000  6,000  7,000Hospitalizations
ICU Admissions
DeathsAREXVY (GSK) ABRYSVO (Pfizer)
(2,200 –7,000)
(330 –1,000)
(200 –1,300)(1,900 –6,300)
(280 –920)
(190 –1,100)
21▪Vaccine Safety Datalink (VSD) rapid cycle analysis signal for immune thrombocytopenic purpura (ITP)1
–VSD identified a statistical signal for ITP in adults ≥60 years who received GSK (AREXVY) RSV
vaccination
•Too early to determine if this represents a true association. After rapid medical record review, most
were found not to be new cases of ITP occurring after RSV vaccination .
▪Co-administration with other vaccines
–Publicly available data on coadministration of GSK AREXVY or Pfizer ABRYSVO with other adult
vaccines remain limited.2,3
–Especially important consideration in older adults recommended to receive multiple vaccines (e.g.,
COVID -19, influenza, pneumococcal, recombinant zoster)Other benefit and harms considerations:
Protein subunit RSV vaccines
Abbreviations: VSD: Vaccine Safety Datalink
1. Donahue J. Presentation at June 2024 ACIP meeting.
2.https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -06-21-23/03 -RSV -Adults -Friedland -508.pdf
3.https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -06-21-23/02 -RSV -Adults -Gurtman -508.pdf
22▪How substantial are the desirable anticipated effects among adults aged ≥75 years?
▪How substantial are the undesirable anticipated effects among adults aged ≥75 years?
▪Do the desirable effects outweigh the undesirable effects among adults aged ≥75 years?Benefits and Harms: Protein Subunit RSV vaccine in adults aged ≥75
years
Minimal Small Moderate Large Varies Don’t know
Minimal Small Moderate Large Varies Don’t know
Favors intervention ( Protein subunit RSV vaccine)
Favors comparison (no vaccine)
Favors both
Favors neither
Unclear
23GRADE Framework: PICO Question
Population Adults aged 60 –74 years at increased risk of severe RSV disease
Intervention RSV Protein Subunit Vaccine:
Pfizer ABRYSVO (1 dose IM) -or-GSK AREXVY (1 dose IM)
Comparison No RSV vaccine
Outcomes ▪RSV lower respiratory tract disease (LRTD)
▪Medically attended RSV LRTD
▪Hospitalization for RSV respiratory illness
▪Severe RSV respiratory illness requiring supplemental oxygen or
other respiratory support
▪Death due to RSV respiratory illness
▪Serious Adverse Events (SAEs)
▪Inflammatory neurologic events (e.g., Guillain -Barré syndrome)
▪Reactogenicity (grade ≥3)
24Summary of GRADE for protein subunit vaccines in adults aged 60 –74 years at
increased risk  of severe RSV disease
Outcome ImportanceDesign
(# of studies)Findings
In adults aged 60 -74 years at increased risk of severe RSV disease:Evidence
type
Benefits
RSV Lower Respiratory
Tract Disease (L TRD)Important RCT (2) Protein subunit RSV vaccination reduces RSV LRTD. High
Medically attended RSV
LRTDCritical RCT (2) Protein subunit RSV vaccination reduces medically attended RSV LRTD. High
Hospitalization for RSV
respiratory illnessCritical RCT (2)Protein subunit RSV vaccination may reduce hospitalization for RSV respiratory
illness.Low
Severe RSV respiratory
illness requiring
O2/respiratory supportImportant RCT (2)Protein subunit RSV vaccination may reduce severe RSV respiratory illness
requiring supplemental oxygen or other respiratory support, but the effect is very
uncertain.Very low
Death due to RSV
respiratory illnessImportant RCT (2) Zero events observedUnable to
evaluate
Harms
Serious adverse events Critical RCT (4) Protein subunit RSV vaccination likely results in little to no difference in SAEs. Moderate
Inflammatory neurologic
eventsCritical RCT (4)Protein subunit RSV vaccination may increase inflammatory neurologic events,
but the effect is very uncertain.Very low
Reactogenicity (grade ≥3) Important RCT (4) Protein subunit RSV vaccination may increase severe reactogenicity events. Low
25Additional information on benefits/harms for protein
subunit vaccines in adults aged 60 –74 years at increased
risk of severe RSV disease
26Per 1 Million Vaccine Doses Administered to Adults Aged 60 –74 Years at
Increased Risk of Severe RSV Disease :
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. FDA self -controlled case series analysis, among CMS Medicare beneficiaries ≥65 years with Parts A, B, and D coverage who did not  have a GBS claim in the 365 days before vaccination. Analysis based on
diagnoses of GBS in inpatient claims data in risk interval (1 -42 days after RSV vaccination) compared to control interval (43 -90 days after RSV vaccination). GBS cases identified using ICD -10 diagnosis of
GBS in primary position of inpatient claims coding. Estimates adjusted for outcome -dependent observation time, positive predicti ve value of diagnostic codes in identifying chart -confirmed GBS cases, and
seasonality. Analysis includes patients with RSV vaccinations  only through October 8, 2023 to allow for 90 -day post -vaccination  observation and 90% or greater claims data completeness. Claims data
through April 6, 2024.
3. Although CMS data were limited to Medicare beneficiaries aged ≥65 years, results are extrapolated here to include adults aged  60-64 years.
4. Self -controlled case series analysis estimated attributable risk of 3 (95% CI: -3, 10) GBS cases. However, the range was truncat ed at zero for Benefit/Risk analyses.Estimated RSV -Associated Outcomes1 Preventable over 2 RSV Seasons  vs. potential cases of GBS
(positive predictive value -adjusted  attributable risk of GBS in FDA -CMS partnership data among adults
aged ≥65 years, 42 -day risk interval2,3)
250 650 2,800
 -  1,000  2,000  3,000  4,000  5,000  6,000  7,000220 580 2,500
 -  1,000  2,000  3,000  4,000  5,000  6,000  7,000Hospitalizations
ICU Admissions
DeathsAREXVY (GSK) ABRYSVO (Pfizer)
3 (range 0–10)4 attributable  cases of GBS 16 (range 3–29) attributable cases of GBS(1,500 –4,700)
(340 –1,070)
(80–440)(1,400 –4,200)
(310 –960)
(70–400)
27Vaccine Primary outcomeEfficacy (95% CI),
months 0 –12aEfficacy (95% CI),
months 13 –24a
Pfizer ABRYSVORSV LRTI with ≥2 lower
respiratory sx62%  (41, 76)
Median 12 months follow -up per
participant55%  (26, 73)
Median 6 months follow -up per
participant
RSV LRTI with ≥3 lower
respiratory sx86%  (63, 96)
Median 12 months follow -up per
participant74%  (27, 92)
Median 6 months follow -up per
participantProtein subunit RSV vaccine efficacy against primary
clinical trial outcomes over time
Abbreviations: CI: confidence interval, LRTI: lower respiratory tract illness, sx: signs or symptoms, LRTD: lower respiratory tract disease
a.Nominal efficacy during 12 -month period. Not all trial participants contributing to estimate had full 12 months’ follow up time during
the period. Median per -participant follow -up time during each period is reported below each estimate.
Pfizer and GSK clinical trials used different primary endpoint definitions and had different follow -up time, so efficacy cannot be
directly compared across trials.
28Vaccine Primary outcomeEfficacy (95% CI),
months 0 –12aEfficacy (95% CI),
months 13 –24a

GSK AREXVYRSV LRTD (≥2 or ≥3
lower respiratory sx)b79%  (58, 90)
Median 12 months follow -up per
participant59%  (34, 75)
Median 12 months follow -up per
participantProtein subunit RSV vaccine efficacy against primary
clinical trial outcomes over time
Abbreviations: CI: confidence interval, LRTI: lower respiratory tract illness, sx: signs or symptoms, LRTD: lower respiratory tract disease
a.Nominal efficacy during 12 -month period. Not all trial participants contributing to estimate had full 12 months’ follow up time during
the period. Median per -participant follow -up time during each period is reported below each estimate.
b.GSK definition of LRTD required ≥2 lower respiratory symptoms or signs (including ≥1 sign), or ≥3 lower respiratory symptoms.
Pfizer and GSK clinical trials used different primary endpoint definitions and had different follow -up time, so efficacy cannot be
directly compared across trials.
29Revaccination with GSK AREXVY at 12 months does not
increase efficacy, compared with a single dose

30▪How substantial are the desirable anticipated effects among adults aged 60 –74 years at increased risk
of severe RSV disease
▪How substantial are the undesirable anticipated effects among adults aged 60 –74 years at increased
risk of severe RSV disease?
▪Do the desirable effects outweigh the undesirable effects among adults aged 60 –74 years at increased
risk of severe RSV disease?Benefits and Harms Protein Subunit RSV vaccine in adults aged 60 –74
years at increased risk of severe RSV disease
Minimal Small Moderate Large Varies Don’t know
Minimal Small Moderate Large Varies Don’t know
Favors intervention ( Protein subunit RSV vaccine)
Favors comparison (no vaccine)
Favors both
Favors neither
Unclear
31GRADE Framework: PICO Question
Population Adults aged ≥75 years
Intervention RSV Vaccine:
Moderna mRESVIA (50μg,single dose IM)
Comparison No RSV vaccine
Outcomes ▪RSV lower respiratory tract disease (LRTD)
▪Medically attended RSV LRTD
▪Hospitalization for RSV respiratory illness
▪Severe RSV respiratory illness requiring supplemental oxygen or
other respiratory support
▪Death due to RSV respiratory illness
▪Serious Adverse Events (SAEs)
▪Inflammatory neurologic events (e.g., Guillain -Barré syndrome)
▪Reactogenicity (grade ≥3)
32Outcome Importance Data SourcesEffect Estimate, Vaccine
Efficacy (95% CI)aConcerns in certainty
assessment
RSV Lower Respiratory Tract
Disease (L TRD)b,c Important
One Phase 2/3 RCT in
adults ≥60 years1
• Mean efficacy follow
up through 18 months
post -vaccination per
participant (median 19
months)d44.0% ( -34.6, 78.2%) Imprecision (serious)e
Medically attended RSV LRTDf,cCritical 39.0% ( -58.8, 78.1%)Indirectness (serious)g
Imprecision (serious)e
Hospitalization for RSV
respiratory illnessf Critical 80.1% ( -363.7, 100%)h Indirectness (serious)f
Imprecision (very serious)i
Severe RSV respiratory illness
requiring O2/respiratory supportImportant No data available Unable to evaluate
Death due to RSV respiratory
illnessd Important Zero events observed Unable to evaluateModerna mRESVIA  in adults aged ≥75 years
Benefits: vaccine efficacy estimates
a) Calculated as (1 –  Incident Rate Ratio) x 100%. Events were included if they occurred >14 days post -vaccination.
b) Included data are from participants aged ≥75 years.
c) LRTD using co -primary endpoint of at LRTD with at least 3 signs or symptoms
d) Efficacy follow -up through maximum 24 months postvaccination per participants (median 19 months)
e) Serious concern for imprecision due to the confidence intervals containing absolute risk reduction estimates for which differ ent policy decisions might be considered.
f) Included data are among all Moderna RCT participants (aged ≥60 years).
g) Serious concern for indirectness due to inclusion of adults aged 60 –74 years.
h) Calculated using 0.5 correction factor to account for zero events in the placebo group. Data cut off April 2023.
i) Serious concern for imprecision due to the confidence intervals containing absolute risk reduction estimates for which differ ent policy decisions might be considered and fragility of the estimate
1. Clinical trials.gov NTC:05127434. https://classic.clinicaltrials.gov/ct2/show/NCT05127434 . Wilson E, Goswami J, Baqui  AH, et al. Efficacy and Safety of an mRNA -Based RSV PreF  Vaccine in Older
Adults. N Engl J Med. 2023 Dec 14;389(24):2233 -2244. doi: 10.1056/NEJMoa2307079. Plus additional data obtained directly from the manufacturer
33Outcome Importance Data SourcesEffect Estimate, Risk ratio
(95% CI)Concerns in certainty
assessment
Serious adverse events
(SAEs)a,b CriticalOne phase 2/3 RCT1,
one phase 1 RCT2 1.00 (0.95, 1.05)Inconsistency (serious)c
Indirectness (serious)d
Inflammatory neurologic
eventsa,e CriticalOne phase 2/3 RCT1,
one phase 1 RCT2 Zero events observed Unable to evaluate
Reactogenicity (grade ≥3)a,fImportantOne phase 2/3 RCT1,
one phase 1 RCT2 1.54 (1.40, 1.68) Indirectness (serious)d
a)Included data are among all Moderna RCT participants (aged ≥60 years).
b)Phase 2/3 RCT: Any time after vaccination. Phase 1 RCT: Within 12 months after vaccination.
c)Serious concern for inconsistency as the risk ratios observed in the phase 1 and phase 2/3 trials had different point estimat es.
d)Serious concern for indirectness due to inclusion of adults aged 60 –74 years.
e)Within 42 days after vaccination
f)Within 7 days after vaccination
1.Clinical trials.gov NTC:05127434. https://classic.clinicaltrials.gov/ct2/show/NCT05127434 . Wilson E, Goswami J, Baqui  AH, et al. Efficacy and Safety of an mRNA -Based RSV
PreF  Vaccine in Older Adults. N Engl J Med. 2023 Dec 14;389(24):2233 -2244. doi: 10.1056/NEJMoa2307079. Plus additional data obtained directly from the manufacturer
2.Clinical trials.gov NTC:04528719. https://clinicaltrials.gov/study/NCT04528719?term=NCT04528719 . Shaw CA, Essink  B, Harper C, et al. Safety and Immunogenicity of an
mRNA -Based RSV Vaccine Including a 12 -Month Booster in a Phase I Clinical Trial in Healthy Older Adults. J Infect Dis. 2024 Feb 22:jiae081. doi: 10.1093/ infdis /jiae081. Epub
ahead of print. PMID: 38385566. Plus additional data obtained directly from the manufacturer, only included those who receive d the phase 2/3 vaccine formulation or placeboModerna mRESVIA  in adults aged ≥75 years
Harms
34Summary of GRADE for Moderna mRESVIA  in adults aged ≥75 years
Outcome ImportanceDesign
(# of studies)FindingsEvidence
type
Benefits
RSV Lower Respiratory Tract
Disease (L TRD)Important RCT (1)Vaccination with Moderna mRESVIA likely reduces RSV LRTD in
adults aged ≥75 years.Moderate
Medically attended RSV LRTD Critical RCT (1)Vaccination with Moderna mRESVIA may reduce medically attended
RSV LRTD in adults aged ≥75 years.Low
Hospitalization for RSV
respiratory illnessCritical RCT (1)Vaccination with Moderna mRESVIA may reduce hospitalization for
RSV respiratory illness in adults aged ≥75 years, but the effect is very
uncertain.Very low
Severe RSV respiratory illness
requiring O2/respiratory
supportImportant RCT (1) No data available to inform this outcomeUnable to
evaluate
Death due to RSV respiratory
illnessImportant RCT (1) Zero events observedUnable to
evaluate
Harms
Serious adverse events Critical RCT (2)Vaccination with Moderna mRESVIA may result in little to no
difference in SAEs in adults aged ≥75 years.Low
Inflammatory neurologic
eventsCritical RCT (2) Zero events observedUnable to
evaluate
Reactogenicity (grade ≥3) Important RCT (2)Vaccination with Moderna mRESVIA likely increases severe
reactogenicity events in adults aged ≥75 years.Moderate
35Additional information on benefits/harms for Moderna
mRESVIA  in adults aged ≥75 years
36▪Data on coadministration with mRESVIA  and other adult vaccines are
limited
▪Coadministration of Moderna mRESVIA  with seasonal quadrivalent
influenza vaccine as well as mRESVIA  with COVID -19 bivalent vaccine met
non -inferiority criteria for immunogenicity.1Other benefit/harms considerations: co -administration
1.https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2024 -02-28-29/02 -RSV -Adults -Das -508.pdf
37▪How substantial are the desirable anticipated effects among adults aged ≥75 years?
▪How substantial are the undesirable anticipated effects among adults aged ≥75 years?
▪Do the desirable effects outweigh the undesirable effects among adults aged ≥75
years?Benefits and Harms Moderna mRESVIA  in adults aged ≥75 years
Minimal Small Moderate Large Varies Don’t know
Minimal Small Moderate Large Varies Don’t know
Favors intervention (Moderna mRESVIA RSV
vaccine)
Favors comparison (no vaccine)
Favors both
Favors neither
Unclear
38GRADE Framework: PICO Question
Population Adults aged 60 –74 years at increased risk of severe RSV disease
Intervention RSV Vaccine:
Moderna mRESVIA (50 μg,single dose IM)
Comparison No RSV vaccine
Outcomes ▪RSV lower respiratory tract disease (LRTD)
▪Medically attended RSV LRTD
▪Hospitalization for RSV respiratory illness
▪Severe RSV respiratory illness requiring supplemental oxygen or
other respiratory support
▪Death due to RSV respiratory illness
▪Serious Adverse Events (SAEs)
▪Inflammatory neurologic events (e.g., Guillain -Barré syndrome)
▪Reactogenicity (grade ≥3)
39Outcome Importance Data SourcesEffect Estimate, Vaccine
efficacy (95% CI)aConcerns in certainty
assessment
RSV Lower Respiratory Tract Disease
(L TRD)b,c Important
One Phase 3 RCT in adults
≥60 years1
• Mean efficacy follow up
through 18 months
post -vaccination per
participant (median 19
months)d66.8% (41.5, 82.1%) None
Medically attended RSV LRTDe,cCritical 39.0% ( -58.8, 78.1%)Indirectness (serious)f
Imprecision (serious)g
Hospitalization for RSV respiratory
illnessc Critical 80.1% ( -363.7, 100%)h Indirectness (serious)f
Imprecision (very serious)i
Severe RSV respiratory illness
requiring O2/respiratory supportc Important Not data available Unable to evaluate
Death due to RSV respiratory illnesscImportant Zero events observed Unable to evaluate
a)Calculated as (1 –  Incident Rate Ratio) x 100%. Events were included if they occurred >14 days post -vaccination.
b)Included data are from participants aged ≥60 years with ≥1 comorbidity (chronic obstructive pulmonary disease [COPD], asthma,  chronic respiratory disease, heart failure,
diabetes mellitus, advanced liver disease, advanced renal disease).
c)LRTD using co -primary endpoint of at LRTD with at least 3 signs or symptoms
d)Efficacy follow -up through maximum 24 months postvaccination per participants (median 19 months)
e)Included data are among all participants (aged ≥60 years).
f)Serious concern for indirectness due to inclusion of adults without comorbidities.
g)Serious concern for imprecision due to the confidence intervals containing absolute risk reduction estimates for which differ ent policy decisions might be considered
h)VE calculated using 0.5 correction factor to account for zero events in the placebo group. Data cut off April 2023
i)Very serious concern for imprecision due to the confidence intervals containing absolute risk reduction estimates for which d ifferent policy decisions might be considered and
fragility of the estimate
1. Clinical trials.gov NTC:05127434. https://classic.clinicaltrials.gov/ct2/show/NCT05127434 . Wilson E, Goswami J, Baqui  AH, et al. Efficacy and Safety of an mRNA -Based RSV PreF  Vaccine in
Older Adults. N Engl J Med. 2023 Dec 14;389(24):2233 -2244. doi: 10.1056/NEJMoa2307079. Plus additional data obtained directly from the manufacturerModerna mRESVIA  vaccine in adults aged 60 –74 years at increased risk of severe RSV disease
Benefits: vaccine efficacy estimates
40a)Included data are among all participants (aged ≥60 years).
b)Phase 2/3 RCT: Any time after vaccination. Phase 1 RCT: Within 12 months after vaccination.
c)Serious concern for inconsistency as the risk ratios observed in the phase 1 and phase 2/3 trials had different point estimat es.
d)Serious concern for indirectness due to inclusion of adults without comorbidities.
e)Within 42 days after vaccination
f)Within 7 days after vaccination
1. Clinical trials.gov NTC:05127434. https://classic.clinicaltrials.gov/ct2/show/NCT05127434 . Wilson E, Goswami J, Baqui  AH, et al. Efficacy and Safety of an mRNA -Based RSV PreF  Vaccine in
Older Adults. N Engl J Med. 2023 Dec 14;389(24):2233 -2244. doi: 10.1056/NEJMoa2307079. Plus additional data obtained directly from the manufacturer
2. Clinical trials.gov NTC:04528719. https://clinicaltrials.gov/study/NCT04528719?term=NCT04528719 . Shaw CA, Essink  B, Harper C, et al. Safety and Immunogenicity of an mRNA -Based RSV
Vaccine Including a 12 -Month Booster in a Phase I Clinical Trial in Healthy Older Adults. J Infect Dis. 2024 Feb 22:jiae081. doi: 10.1093/ infdis /jiae081. Epub  ahead of print. PMID: 38385566.
Plus additional data obtained directly from the manufacturer, only included those who received the phase 2/3 vaccine formulat ion or placeboOutcome Importance Data Sources Effect Estimate, Risk
ratio (95% CI)Concerns in certainty
assessment
Serious adverse events
(SAEs)a,bCriticalOne phase 2/3 RCT1,
one phase 1 RCT2 1.00 (0.95, 1.05)Inconsistency (serious)c
Indirectness (serious)d
Inflammatory
neurologic eventsa,eCriticalOne phase 2/3 RCT1,
one phase 1 RCT2 Zero events observed Unable to evaluate
Reactogenicity (grade
≥3)a,fImportantOne phase 2/3 RCT1,
one phase 1 RCT2 1.54 (1.40, 1.68) Indirectness (serious)dModerna mRESVIA  vaccine in adults aged 60 –74 years at increased risk
of severe RSV disease
Harms
41Summary of GRADE for Moderna mRESVIA  vaccine in adults aged 60 –74
years at increased risk of severe RSV disease
Outcome ImportanceDesign
(# of studies)FindingsEvidence
type
Benefits
RSV Lower Respiratory Tract
Disease (LTRD)Important RCT (1)Vaccination with Moderna mRESVIA reduces RSV LRTD in adults aged 60 –
74 years at increased risk of severe RSV disease.High
Medically attended RSV LRTD Critical RCT (1)Vaccination with Moderna mRESVIA may reduce medically attended RSV
LRTD in adults aged 60 –74 years at increased risk of severe RSV disease.Low
Hospitalization for RSV
respiratory illnessCritical RCT (1)Vaccination with Moderna mRESVIA may reduce hospitalization for RSV
respiratory illness in adults aged 60 –74 years at increased risk of severe
RSV disease, but the effect is very uncertain.Very low
Severe RSV respiratory illness
requiring O2/respiratory
supportImportant RCT (1) No data available to inform this outcomeUnable to
evaluate
Death due to RSV respiratory
illnessImportant RCT (1) Zero events observedUnable to
evaluate
Harms
Serious adverse events Critical RCT (2)Vaccination with Moderna mRESVIA may result in little to no difference in
SAEs in adults aged 60 –74 years at increased risk of severe RSV disease.Low
Inflammatory neurologic events Critical RCT (2) Zero events observedUnable to
evaluate
Reactogenicity (grade ≥3) Important RCT (2)Vaccination with Moderna mRESVIA likely increases severe reactogenicity
events in adults aged 60 –74 years at increased risk of severe RSV disease.Moderate
42Primary outcomeEfficacy (95% CI),
months 0 –12aEfficacy (95% CI),
months 12 –24a
RSV LRTD with ≥2 lower
respiratory signs or
symptoms56%  (42, 67)
Mean 12 months follow -up per participant30%  (1, 51)
Mean 7 months follow -up per participant
RSV LRTD with ≥3 lower
respiratory signs or
symptoms55%  (31, 71)
Mean 12 months follow -up per participant36%  (-13, 64)
Mean 7 months follow -up per participantModerna mRESVIA  vaccine efficacy against primary clinical
trial outcomes over time
Abbreviations: CI: confidence interval, LRTD: lower respiratory tract disease
a.Nominal efficacy during 12 -month period. Not all trial participants contributing to estimate had full 12 months’ follow up time during the period. Mean
per-participant follow -up during each period (reported below each estimate) was calculated by CDC using number of participants a nd total person -time
provided by manufacturer.
43▪How substantial are the desirable anticipated effects among adults aged 60 –74 years at increased risk
of severe RSV disease?
▪How substantial are the undesirable anticipated effects among adults aged 60 –74 years at increased
risk of severe RSV disease?
▪Do the desirable effects outweigh the undesirable effects among adults aged 60 –74 years at increased
risk of severe RSV disease?Benefits and Harms Moderna mRESVIA  in adults aged 60 –74 years at
increased risk of severe RSV disease
Minimal Small Moderate Large Varies Don’t know
Minimal Small Moderate Large Varies Don’t know
Favors intervention (Moderna mRESVIA RSV
vaccine)
Favors comparison (no vaccine)
Favors both
Favors neither
Unclear
44
Values and preferences
- Do adults 75 and older feel the desirable effects of RSV vaccination are large relative to the
undesirable effects?
- Do adults 60 –74 at increased risk of severe RSV disease feel the desirable effects of RSV vaccination
are large relative to the undesirable effects?
- Is there important variability in how these adults value the main outcomes?
456.5
10.6
10.712.2
17.1
25.132.7
41.0
33.148.6
31.2
31.1
0 25 50 75 100Age ≥75 (N=326)Age 60 -74 (N=977)Age 18 -59 (N=2,799)
Weighted %Very concerned Moderately concerned A little concerned Not at all concernedConcern about Getting RSV Disease Among Adults ≥60 Years of Age, by
Age Group, Omnibus Surveys, April 4 –26, 2024 (N=4,102)
Omnibus Surveys: data for this analysis were collected through the Ipsos KnowledgePanel  and NORC AmeriSpeak  Omnibus Surveys, which use probability -based panels to survey a nationally representative
sample of U.S. adults aged 18 years and older. CDC fields questions about vaccination status, intent, knowledge, attitudes, b eliefs, and behaviors on each survey for 2 waves each month, for a combined sample
size of ~4,000 respondents. These slides present results from April 2024. Data were weighted to represent the non -institutionali zed U.S. population and mitigate possible non -response bias. All responses are self -
reported.
46RSV Vaccination Among Adults ≥60 Years of Age, by Age Group
September 2023 –May 2024 (n=156,281)
National Immunization Survey -Adult COVID Module (NIS -ACM)
National Immunization Survey -Adult COVID Module (NIS -ACM). The NIS -ACM is a random -digit -dial cellular telephone survey of adults age ≥18 years in the U.S. Respondents
are sampled within all 50 states, District of Columbia, five local jurisdictions (Bexar County TX, Chicago IL, Houston TX, Ne w York City NY, and Philadelphia County PA), Guam,
Puerto Rico, and the U.S. Virgin Islands (sampled in 2023 only). Data are weighted to represent the non -institutionalized U.S. p opulation. All responses are self -reported.
https://www.cdc.gov/vaccines/imz -managers/coverage/rsvvaxview/adults -60-coverage -intent.html  24.430.732.3
18.1
010203040Vaccinated with RSV vaccine (%)
Week end dateAll adults 60+ 80+ 70-79 60-69
47▪While we do not have any data specifically looking at how adults value estimated
protection against RSV in relation to potential risk of GBS, a few considerations:
1.Adults are willing to accept some rate of vaccine -associated adverse events for the
benefit of preventing disease1
2.Individual baseline and vaccine -associated risk of GBS may differ by age group and
presence of chronic conditions
3.Willingness to accept risk of GBS after vaccination may differ by age and health
status and perceived risk of RSV -associated disease2Risk of Guillain -Barre Syndrome (GBS)
1.Scherer LD, Shaffer VA, Patel N, Zikmund -Fisher BJ. Can the vaccine adverse event reporting system be used to increase vaccine a cceptance and trust? Vaccine. 2016 May
5;34(21):2424 -2429.  https://pubmed.ncbi.nlm.nih.gov/27049120/
2.Prosser LA, Payne K, Rusinak  D, et al. Valuing health across the lifespan: health state preferences for seasonal influenza illnesses in patients of differ ent ages. Value Health.
2011;14(1):135 -143.  https://pubmed.ncbi.nlm.nih.gov/21211495/
48▪In the first RSV season after ACIP made a shared clinical decision -making
recommendation for adults 60 years and older, an estimated 20 –30% of U.S. adults in
this age group received RSV vaccination.
▪Vaccination uptake was higher among adults ≥70 years than among adults 60 –69 years.
▪We do not have data on how adults value risk of protection against RSV versus
potential risk of GBS , but this may vary by age or other factors. Values: summary of the available evidence
Adults 60 years and older
49▪Do adults aged ≥75 years feel that the desirable effects of RSV
vaccination are large relative to the undesirable effects?
▪Is there important uncertainty about, or variability in, how much adults
aged ≥75 years value the main outcomes?Values
No Probably no Probably Yes Yes Varies Don’t know
Important uncertainty or variability
Probably important uncertainty or variability
Probably not important uncertainty or variability
No important uncertainty or variability
No known undesirable outcomes
50▪Do adults aged 60 –74 years at increased risk of severe RSV disease feel
that the desirable effects of RSV vaccination are large relative to the
undesirable effects?
▪Is there important uncertainty about, or variability in, how much adults
aged 60 –74 years at increased risk of severe RSV disease value the main
outcomes?Values
No Probably no Probably Yes Yes Varies Don’t know
Important uncertainty or variability
Probably important uncertainty or variability
Probably not important uncertainty or variability
No important uncertainty or variability
No known undesirable outcomes
51
Is it feasible to implement RSV vaccination for adults 75 and older ?
Is it feasible to implement RSV vaccination for adults 60 –74 at increased risk of severe RSV disease ?Acceptability
Would recommending RSV vaccination for adults 75 and older be acceptable to key stakeholders?
Would recommending RSV vaccination for adults 60 –74 at increased risk of severe RSV disease
be acceptable to key stakeholders?
Feasibility
52Based on survey data, physicians think shared clinical decision -making
increases time and confusion1
Kempe A, Lindley MC, O'Leary ST, et al. Shared Clinical Decision -Making Recommendations for Adult Immunization: What Do Physicia ns Think? J Gen Intern
Med . 2021;36(8):2283 -2291. https://pubmed.ncbi.nlm.nih.gov/33528783/  . Numbers cited based on General Internal Medicine physician responses, N=281). 68% strongly agreed
SCDM will require more
time with patients 44% either strongly or
somewhat agreed they find
it hard to explain what a
SCDM recommendation
means to patients
76% either strongly or
somewhat agreed SCDM
creates confusion42% either strongly or
somewhat agreed they
did not know how to
implement SCDM as
intended by the ACIP
53▪ SCDM conversations are challenging and time -consuming.
▪ Compared to universal recommendations, SCDM does not have a clear call to
action.
▪ Standing orders - often used by medical assistants, nurses, and pharmacists – are
difficult under SCDM .
▪ Approximately 80%  of all older adult RSV vaccinations have been given in
pharmacies. Not all providers who give vaccines are comfortable with the SCDM
conversation or feel it is within their scope of practice.
▪ In the specific instance of RSV vaccines, there are also concerns about the ability to
complete the type of risk -benefit discussion intended by ACIP with the RSV SCDM
recommendation.CDC and ACIP have heard feedback that the RSV SCDM
recommendation has been difficult to implement
Dr. Carla Black, ACIP Meeting February 2024: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2024 -02-28-29/04 -RSV -Adults -Black -508.pdf
54▪Vaccine acquisition cost relatively high
–Costly upfront investment to carry RSV vaccines
▪RSV vaccine billed under Medicare  Part D
–Millions of Medicare beneficiaries are not enrolled in Part D
–Part D generally described as more challenging to access and implement
than Part B so providers may be less likely to carry vaccine in their
practices and instead refer to pharmaciesFinancial and insurance barriers
55▪Multiple adult RSV vaccine products
▪Different storage and handling requirements
–Moderna mRESVIA  requires frozen storage or if refrigerated use within
30 days
▪Adult vaccine schedule is increasingly complex including
multiple products with different schedulesSchedule complexity
56Acceptability and Feasibility: Summary of the available evidence
All adults aged 75 years and older
•Makes vaccination the “default”
•Easier to incorporate into standing
orders, clinical decision support, and
messaging
•Covers those at highest risk without
asking providers to do extensive
individualized risk assessment•“Universal” RSV recommendation
only for some ages
•Ongoing challenge in complexity
of adult schedule
•Repeated recommendation
changes may cause confusion
57Acceptability and Feasibility: Summary of the available evidence
Risk -based recommendation adults aged 60 –74 years
•Compared with a shared clinical
decision -making recommendation, a
risk-based recommendation will
provide more clarity to providers and
public about who should  get an RSV
vaccine
•Easier to incorporate into standing
orders, clinical decision support,  and
messaging•Risk -based recommendations are
still more challenging to
implement than universal
recommendations
•Eligible risk factors for RSV
vaccination will not align with
other adult vaccines
•Repeated recommendation
changes may cause confusion
58▪Would recommending RSV vaccines for adults aged ≥75 years
be acceptable to key stakeholders?
▪Would recommending RSV vaccines for adults aged 60 –74
years at increased risk of severe RSV disease be acceptable to
key stakeholders?Acceptability
No Probably No Probably Yes Yes Varies Don’t know
No Probably No Probably Yes Yes Varies Don’t know
59▪Is it feasible to implement protein subunit RSV vaccination
among  adults aged ≥75 years?
▪Is it feasible to implement Moderna mRESVIA  vaccination
among adults aged ≥75 years?Feasibility
No Probably No Probably Yes Yes Varies Don’t know
No Probably No Probably Yes Yes Varies Don’t know
60▪Is it feasible to implement protein subunit RSV vaccination
among adults aged 60 –74 years at increased risk of severe
RSV disease?
▪Is it feasible to implement Moderna mRESVIA  vaccination
among adults aged 60 –74 years at increased risk of severe
RSV disease?Feasibility
No Probably No Probably Yes Yes Varies Don’t know
No Probably No Probably Yes Yes Varies Don’t know
61
Resource Use
Is an RSV vaccine program for adults a reasonable and efficient allocation
of resources for:
•Adults 75 and older?
•Adults 60 –74 at increased risk of severe RSV disease?
62▪RSV vaccination is likely cost -effective for:
–Adults aged 75 years and older
–Adults aged 60 –74-year with risk factors for severe RSV disease
▪RSV vaccination is likely NOT cost -effective in adults aged 60 –74 years without  risk
factors.
–Therefore, a universal  RSV vaccination in adults aged 60 –74 years is likely NOT a reasonable and efficient allocation
of societal resources
▪There remains substantial uncertainty in key parameters that impact cost
effectiveness:
–Uncertainty in incidence of medically attended RSV illness, particularly hospitalizations
–Uncertainty in RSV -attributable mortality
–Uncertainty in duration of protection from a single dose of RSV vaccination
–Real -world vaccine effectiveness of Moderna mRESVIA ; analyses currently rely on clinical trial efficacy estimates
▪For all 3 manufacturers, Work Group felt that if RSV vaccine list prices were
substantially reduced, then RSV vaccination may be a cost -effective intervention for
a broader adult population.Work Group considerations regarding societal resource use
toward RSV vaccination in older adults at current list prices
63▪Is protein subunit RSV vaccination a reasonable and efficient allocation of resources
in adults aged ≥75 years ?
▪Is Moderna mRESVIA  vaccination  in adults  aged ≥75 years a reasonable and efficient
allocation of resources?Resource use
No Probably No Probably Yes Yes Varies Don’t knowNo Probably No Probably Yes Yes Varies Don’t know
64▪Is protein subunit RSV  vaccination a reasonable and efficient allocation of resources
in adults aged 60 –74 years at increased risk of severe RSV disease ?
▪Is Moderna mRESVIA  vaccination  in adults aged 60 –74 years at increased risk of
severe RSV disease a reasonable and efficient allocation of resources?Resource use
No Probably No Probably Yes Yes Varies Don’t knowNo Probably No Probably Yes Yes Varies Don’t know
65
Equity
What would be the impact on health equity of recommending RSV
vaccination for:
•Adults 75 and older?
•Adults 60 –74 at increased risk of severe RSV disease?
66Median age of non -pregnant adults aged ≥18 years with RSV -associated
hospitalizations by race and ethnicity* — RSV-NET, 2014 –2015 to 2022 –
2023
UnweightedWeighted
%Median
AgeInterquartile
range (IQR)
Overall 17,847 - 69 (58–81)
White 10,755 62.2 73 (63-82)
Black 3,529 20.4 62 (50-71)
Hispanic 1,434 8.3 62 (48-76)
Asian or Pacific Islander 1,020 5.9 73 (59-83)
American Indian or Alaska
Native90 0.5 64 (54-73)
Multiple races 89 0.5 75 (58-84)
Unknown 367 2.1 68 (57-78)
*Black, White, American Indian/Alaska Native and Asian/Pacific Islander people were categorized as non -Hispanic; Hispanic people  could be of any race.Median age of
hospitalization is
lower among Black,
Hispanic, and
American
Indian/Alaska Native
persons than White
and Asian/Pacific
Islander persons.
67050100150200250300350400450500
Age 60 –74 years Age ≥75 yearsRSV -associated hospitalizations per
100,000 populationBlack
Hispanic
White
Asian & Pacific IslanderRSV -associated hospitalization rates by age group and race
and ethnicity*, RSV -NET, 2018 –2019
https://www.cdc.gov/rsv/research/rsv -net/index.html  Unpublished data. Rates are adjusted using multipliers for the frequency of RSV testing during each season and the sensitivit y of RSV
diagnostic tests. Error bars represent 95% confidence intervals. Estimated rates exclude recorded hospitalizations among preg nan t adults. Black, White, and Asian/Pacific Islander people
were categorized as non -Hispanic; Hispanic people could be of any race. Hospitalization rates among American Indian and Alaska N ative persons are not shown due to small numbers. There
may be unmeasured confounding, especially in the oldest age group. Although incidence appears lower in Black adults 75 and ol der than in White adults, if Black adults are less likely to
survive to age 80 or 90 years, then differences in underlying age distribution may be driving this finding. Black adults had a
hospitalization rate 1.5x
higher than White adults
68Weekly cumulative RSV vaccination coverage, by race and ethnicity,
Medicare fee -for-service beneficiaries aged ≥65 years and enrolled in a Part
D plan, United States
Data source: C enters for Medicare & Medicaid Services Chronic Conditions Warehouse. Estimates are based on data released by CMS through Mar ch 30, 2024. Overall includes persons categorized as ‘Unknown’
for race and ethnicity category. Data can be accessed at : https://www.cdc.gov/vaccines/imz -managers/coverage/rsvvaxview/adults -65yrs -older -coverage.html  0510152025
8/5/2023
8/12/2023
8/19/2023
8/26/2023
9/2/2023
9/9/2023
9/16/2023
9/23/2023
9/30/2023
10/7/2023
10/14/2023
10/21/2023
10/28/2023
11/4/2023
11/11/2023
11/18/2023
11/25/2023
12/2/2023
12/9/2023
12/16/2023
12/23/2023
12/30/2023
1/6/2024
1/13/2024
1/20/2024
1/27/2024
2/3/2024
2/10/2024
2/17/2024
2/24/2024
3/2/2024
3/9/2024
3/16/2024
3/23/2024
3/30/2024White, Non-
Hispanic
Overall
Asian, Non-
Hispanic
Black, Non-
Hispanic
Hispanic
6936.1*29.8*22.5*18.020.8*28.4*23.7*14.87.0*24.519.324.5*24.9*30.923.9*26.625.322.0*25.921.6*26.118.3*27.5
0 5 10 15 20 25 30 35 40 45Advanced degreeCollege graduateSome collegeHigh school or less (Ref)Income unknownAbove poverty, >=$75KAbove poverty, <$75KBelow poverty (Ref)UninsuredInsured (Ref)Rural (Ref)SuburbanUrbanHHS Region 10HHS Region 9HHS Region 8HHS Region 7HHS Region 6HHS Region 5HHS Region 4HHS Region 3HHS Region 2HHS Region 1 (Ref)
Weighted % (95% CI)RSV Vaccination Coverage Among Adults ≥60 Years of Age, by end of
March 2024 (n=156,281)
National Immunization Survey -Adult COVID Module (NIS -ACM)
Vaccination coverage was
significantly lower among
adults in rural areas
(19.3%), uninsured  (7.0%),
those with lower
household income , and
with educational level of
high school or less (18.0%).
HHS Regions
1: CT,ME,MA,NH,RI,VT
2: NJ,NY,PR,VI
3: DE,DC,MD,PA,VA,WV
4: AL,FL,GA,KY,MS,NC,SC,TN
5: IL,IN,MI,MN,OH,WI
6: AR,LA,NM,OK,TX
7: IA,KS,MO,NE
8: CO,MT,ND,SD,UT,WY
9: AZ,CA,HI,NV,GU
10: AK,ID,OR,WACI: 95% confidence interval; Ref: Referent category.
*Statistically significant at p<0.05 compared to the referent category.
Kaplan -Meier estimates are based on cumulative data through April 27, 2024.
70Equity:  Summary of the available evidence
All adults aged 75 years and older
•Practicality and value of issuing
a simple and clear message
may remove barriers  to
vaccination
•Adults with undiagnosed
chronic medical conditions
would be included in the
recommendation•Universal recommendations do
not guarantee equity; even if
coverage increases across all
groups, disparities between
groups may remain
71Equity:  Summary of the available evidence
Adults aged 60 –74 years at increased risk of severe RSV
disease
•Clarifying who is at risk may
remove barriers   to vaccination
•May increase coverage among
racial/ethnic minority groups in
whom prevalence of chronic
conditions is higher in 60 –74
age group•Adults with undiagnosed
chronic medical conditions may
be deemed ineligible for
vaccination under a risk -based
recommendation; under shared
clinical decision -making, some
of these adults may have
obtained RSV vaccination
72▪What would be the impact on health
equity of recommending RSV vaccination
in adults aged ≥75 years?▪What would be the impact on health
equity of recommending RSV vaccination
in adults aged 60 –74 years at increased
risk of severe RSV disease?Equity
Reduced
Probably reduced
Probably no impact
Probably increased
Increased
Varies
Don’t knowReduced
Probably reduced
Probably no impact
Probably increased
Increased
Varies
Don’t know
73
Summary
74Domain Question Work Group Judgements
Adults aged 75 years and older Protein Subunit
RSV Vaccines
(Pfizer and GSK)Moderna
Public Health
ProblemIs RSV of public health importance? Yes
Benefits and
HarmsHow substantial are the desirable anticipated effects? Moderate/Large Moderate/Large
How substantial are the undesirable anticipated effects? Small/Moderate Small
Do the desirable effects outweigh the undesirable effects? Favors intervention Favors intervention
ValuesDoes the target population feel the desirable effects are large
relative to the undesirable effects?Yes/Probably yes
Is there important variability in how patients value the
outcomes?Probably not important variability
Acceptability Is the intervention acceptable to key stakeholders? Yes
Feasibility Is the intervention feasible to implement? Yes/Probably yes Yes/Probably yes
Resource UseIs the intervention a reasonable and efficient allocation of
resources?Yes/Probably yes Yes/Probably yes
Equity What would be the impact on health equity? Increased/Probably increased
75Domain Question Work Group Judgements
Adults aged 60–74 years at increased risk of
severe RSV disease Protein Subunit
RSV Vaccines
(GSK and Pfizer)Moderna
Public Health
ProblemIs RSV of public health importance? Yes
Benefits and
HarmsHow substantial are the desirable anticipated effects? Moderate/Large Moderate/Large
How substantial are the undesirable anticipated effects? Small/Moderate Small
Do the desirable effects outweigh the undesirable effects? Favors intervention Favors intervention
ValuesDoes the target population feel the desirable effects are large
relative to the undesirable effects?Probably yes
Is there important variability in how patients value the
outcomes?Probably not important variability
Acceptability Is the intervention acceptable to key stakeholders? Yes/Probably yes
Feasibility Is the intervention feasible to implement? Yes/Probably yes Yes/Probably yes
Resource UseIs the intervention a reasonable and efficient allocation of
resources?Yes/Probably yes Yes/Probably yes
Equity What would be the impact on health equity? Probably increased
76▪The shared clinical decision -making (SCDM) recommendation was made in the setting of
uncertainty about both the estimated benefits and potential risks of RSV vaccination.
▪Now there is real -world evidence of robust protection against RSV -associated hospitalization
during the first season after vaccination among adults 60 and older, including among adults 75
and older and adults with chronic medical conditions.
▪On the other hand, uncertainty remains regarding the magnitude of potential risk of Guillain -
Barre syndrome (GBS).
▪The Work Group believes the GBS signal continues to warrant close attention and additional
follow -up.
▪A transition from SCDM to a universal recommendation among adults 75 years and older
and a risk -based recommendation among adults aged 60 –74 years and is intended to:
–Maximize vaccination among persons most likely to benefit among whom we now have
real -world evidence of protection
–Minimize vaccination among persons least likely to benefit  while additional safety data
accrueWork Group Considerations
77▪The Work Group discussed the role of potential preferential recommendations
between products, but felt that the strength of the available evidence did not
meet the standard for a preferential recommendation at this time.
▪Reasons cited included:
–Current safety analyses are interim and based on a small numbers of GBS cases.
–Unknown relative duration of protection across products
–Need for revaccination and potential risk of GBS associated with additional
doses unknown
–Changes based on limited evidence may have unintended programmatic
consequences Additional Work Group discussions
78Evidence to Recommendations Framework
Summary: Work Group Interpretations
Balance of
consequencesUndesirable
consequences
clearly outweigh
desirable
consequences in
most settingsUndesirable
consequences
probably
outweigh
desirable
consequences in
most settingsThe balance
between
desirable and
undesirable
consequences is
closely balanced
or uncertainDesirable
consequences
probably
outweigh
undesirable
consequences in
most settingsDesirable
consequences
clearly outweigh
undesirable
consequences in
most settingsThere is
insufficient
evidence to
determine the
balance of
consequences
Balance of
consequencesUndesirable
consequences
clearly outweigh
desirable
consequences in
most settingsUndesirable
consequences
probably
outweigh
desirable
consequences in
most settingsThe balance
between
desirable and
undesirable
consequences is
closely balanced
or uncertainDesirable
consequences
probably
outweigh
undesirable
consequences in
most settingsDesirable
consequences
clearly outweigh
undesirable
consequences in
most settingsThere is
insufficient
evidence to
determine the
balance of
consequencesAmong adults aged 60–74 years at increased risk of severe RSV disease :Among all adults aged ≥75 years :
79Evidence to Recommendations Framework
Summary: Work Group Interpretations – Is there sufficient information to move
forward with a recommendation?
Among adults aged 60–74 years at increased risk of severe RSV disease :Among all adults aged ≥75 years :
Yes NoYes No
80Evidence to Recommendations Framework
Summary: Work Group Interpretations
Type of recommendation, all adults aged ≥75 years
•We recommend the intervention
Type of recommendation, adults aged 60 –74 years at increased risk of severe RSV
disease
•We recommend the intervention
811.ACIP recommends adults 75 years of age and older receive a single dose
of RSV vaccine.a,b
2.ACIP recommends adults 60 –74 years of age who are at increased risk of
severe RSV diseasec receive a single dose of RSV vaccine.a,bProposed ACIP vote language
a.RSV vaccination is recommended as a single lifetime dose only. Persons who have already received RSV vaccination
are NOT recommended to receive another dose.
b.These recommendations would supplant the current recommendation that adults 60 years of age and older may
receive RSV vaccination, using shared clinical decision -making. Adults 60 –74 years of age who are not at increased
risk of severe RSV disease would NOT be recommended to receive RSV vaccination.
c.CDC will publish Clinical Considerations that describe chronic medical conditions and other risk factors for severe
RSV disease for use in this risk -based recommendation.
82
Should adults aged 50 –59 years at increased
risk of severe RSV disease  be recommended
to receive a single dose of RSV vaccination?
83
EtR  Domain: Public Health Problem
Is the problem of public health importance among adults aged 50 –59 years
at increased risk of severe RSV disease?
84Estimated annual number  of
RSV-associated
hospitalizations * among
adults aged ≥18 years by age
group and year, RSV -NET,
2016 –17 to 2019 –20
0 20,000 40,000 60,000 80,000 100,000≥80
75–79
70–74
65–69
60–64
55–59
50–54
18–49
Annual RSV -associated hospitalizationsAge
group,
years2016 –17 2017 –18 2018 –19 2019 –20
Preliminary unpublished data. Hospitalization counts  are adjusted
using multipliers for the frequency of RSV testing during each season
and the sensitivity of RSV diagnostic tests. Error bars represent 95%
confidence intervals.
*Estimated hospitalizations exclude recorded hospitalizations among
pregnant adults.
https://www.cdc.gov/rsv/research/rsv -net/index.html  Estimated  10,000 – 20,000
annual RSV -associated
hospitalizations  in
U.S. adults aged 50–59 yearsSurveillance
season:
85RSV -associated hospitalization rates among community -dwelling adults
aged ≥50 years with chronic medical conditions, 2017 –2018 season
BMI: Body Mass Index (kg/m2), COPD: Chronic Obstructive Pulmonary Disease. Data are preliminary and unpublished. Rates of laboratory -confirmed RSV -associat ed hospitalization account for under -detection of RSV infection among hospitalized adults and
sensitivity of diagnostic tests. Poisson regression using Monte Carlo simulation estimated rates and 95% confidence intervals  (represented by error bars). Rates for community -dwelling adults exclude residents of nursing homes and long -term care facilities
and are not adjusted for sex or race/ethnicity group.0200400600
50–59
60–74
≥75
50–59
60–74
≥75
50–59
60–74
≥75
50–59
60–74
≥75
50–59
60–74
≥75
50–59
60–74
≥75
50–59
60–74
≥75
50–59
60–74
≥75
50–59
60–74
≥75
50–59
60–74
≥75
None of
These
ConditionsChronic
Kidney
DiseaseCOPD Severe
obesity
(BMI ≥40)Asthma Coronary
Artery
DiseaseDiabetes
mellitusStroke Obesity
(BMI 30 –
39)Current
smokerRSV-associated hospitalization rate
(per 100,000)
Community -dwelling adults
with none of these conditionsCommunity -dwelling adults
with each condition
////////
//////////////////
86▪Is RSV of public health importance among adults aged 50–59
years at increased risk of severe RSV disease? Public Health Problem: Work Group interpretation
NoProbably
NoProbably
YesYes VariesDon’t
know
87
EtR  Domain: Benefits and Harms 50 –59
- How substantial are the desirable anticipated effects?
- How substantial are the undesirable anticipated effects?
- Do the desirable effects outweigh the undesirable effects?
88GRADE Framework: PICO Question
Population Adults aged 50 –59 at increased risk of severe RSV disease
Intervention RSV Vaccine:
GSK AREXVY (1 dose IM)
Comparison No RSV vaccine
Outcomes ▪RSV lower respiratory tract disease (LRTD)
▪Medically attended RSV LRTD
▪Hospitalization for RSV respiratory illness
▪Severe RSV respiratory illness requiring supplemental oxygen or other
respiratory support
▪Death due to RSV respiratory illness
▪Serious Adverse Events (SAEs)
▪Inflammatory neurologic events (e.g., Guillain -Barré syndrome)
▪Reactogenicity (grade ≥3)
89a) The manufacturer calculated GMR as Cohort 2 / Cohort 1a. However, here, the reciprocal is shown: Cohort 1a / Cohort 2. GMR va lues >1 indicate higher
GMTs in Cohort 1a (adults 50 –59 at increased risk), compared with Cohort 2 (adults ≥60).
b) Noninferiority objective was lower bound of the confidence interval ≥0.67, when evaluating the GMR Cohort 1a / Cohort 2.
c) Serological assays for the determination of antibodies against RSV -A are performed by neutralization assay. The corresponding an tibody titers were
expressed in ED60 (serum estimated dilution inducing 60% inhibition in plaque -forming units). Assessed at Day 31 , where Day 1 w as day of vaccination
d) Serological assays for the determination of antibodies against RSV -B are performed by neutralization assay. The corresponding an tibody titers were
expressed in ED60. Assessed at Day 31 , where Day 1 was day of vaccination.
1. https://clinicaltrials.gov/study/NCT05590403 , https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -10-25-26/02 -gerber -adult -RSV -
508.pdf , unpublished data obtained from manufacturern GMT (95% CI),
30 days post -vaccinationn GMT (95% CI),
30 days post -vaccinationGMR (95% CI)a,
Cohort 1a vs.
Cohort 2Met
Noninferiority
Objectiveb
Cohort 1a: Adults aged 50 –59 years at
increased risk of severe RSV diseaseCohort 2: Adults aged ≥60 years
RSV-Ac343 8922.7 (8118.2, 9806.9) 342 7440.1 (6768.4, 8178.5) 1.20 (1.05, 1.37) Yes
RSV-Bd343 10054.7 (9225.4, 10958.7) 341 8062.8 (7395.9, 8789.9) 1.25 (1.10, 1.41) Yes
Abbreviations: CI = confidence interval; GMT = geometric mean titer; GMR = geometric mean ratioGSK AREXVY vaccine in adults aged 50 –59 years at increased risk of severe RSV disease
Benefits: Geometric Mean Ratio (GMR) of neutralizing antibody titers1
90Summary of GRADE for GSK AREXVY in adults aged 50 –59 years at increased risk of
severe RSV disease
Outcome ImportanceDesign
(# of
studies)Findings
In adults aged 50 -59 years at increased risk of severe RSV disease:Evidence
type
Benefits
RSV Lower Respiratory
Tract Disease (L TRD)Important RCT (1) Vaccination with GSK AREXVY likely reduces RSV LRTD Moderate
Medically attended RSV
LRTDCritical RCT (1) Vaccination with GSK AREXVY likely reduces medically attended RSV LRTD Moderate
Hospitalization for RSV
respiratory illnessCritical RCT (1)Vaccination with GSK AREXVY may reduce hospitalization for RSV respiratory
illnessVery Low
Severe RSV respiratory
illness requiring
O2/respiratory supportImportant RCT (1)Vaccination with GSK AREXVY may reduce severe RSV respiratory illness
requiring supplemental O2 or other respiratory supportVery Low
Death due to RSV
respiratory illnessImportant RCT (1) Zero events observedUnable to
evaluate
Harms
Serious adverse events Critical RCT (1)Vaccination with GSK AREXVY may result in little to no difference in serious
adverse eventsLow
Inflammatory neurologic
eventsCritical RCT (1) Zero events observedUnable to
evaluate
Reactogenicity (grade ≥3) Important RCT (1) Vaccination with GSK AREXVY increases severe reactogenicity events Moderate
91Additional information on benefits/harms for adults aged
50–59 years at increased risk of severe RSV disease
92Per 1 Million Doses of GSK AREXVY Administered to Adults Aged 50 –59
Years at Increased Risk of Severe RSV Disease :
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. FDA self -controlled case series analysis, among CMS Medicare beneficiaries ≥65 years with Parts A, B, and D coverage who did not  have a GBS claim in the 365 days before vaccination. Analysis based on
diagnoses of GBS in inpatient claims data in risk interval (1 -42 days after RSV vaccination) compared to control interval (43 -90 days after RSV vaccination). GBS cases identified using ICD -10 diagnosis of
GBS in primary position of inpatient claims coding. Estimates adjusted for outcome -dependent observation time, positive predicti ve value of diagnostic codes in identifying chart -confirmed GBS cases, and
seasonality. Analysis includes patients with RSV vaccinations  only through October 8, 2023 to allow for 90 -day post -vaccination  observation and 90% or greater claims data completeness. Claims data
through April 6, 2024.
3. Although CMS data were limited to Medicare beneficiaries aged ≥65 years, results are extrapolated here to adults aged 50 -59 year s.
4. Self -controlled case series analysis estimated attributable risk of 3 (95% CI: -3, 10) GBS cases. However, the range was truncat ed at zero for Benefit/Risk analyses.Estimated RSV -Associated Outcomes1 Preventable over 2 RSV Seasons  vs. potential cases of GBS
(positive predictive value -adjusted  attributable risk of GBS in FDA -CMS partnership data among adults
aged ≥65 years, 42 -day risk interval2,3)
3 (range 0–10)4 attributable  cases of GBS80 330 1,500
 -  1,000  2,000  3,000  4,000  5,000  6,000  7,000Hospitalizations
ICU Admissions
Deaths
(30–200)(130 –800)(600 –3,700)
93▪Revaccination at 12 months does not appreciably increase efficacy, compared with a
single dose.
▪Optimal timing of re -vaccination is unknown.
▪No available clinical trial immunogenicity, efficacy, or safety data in severely immune
compromised persons (e.g., hematopoietic cell or solid organ transplant recipients).As reviewed for adults 60 and older, there are a number of
additional considerations
94▪How substantial are the desirable anticipated effects among adults aged 50 –59 years at increased risk
of severe RSV disease
▪How substantial are the undesirable anticipated effects among adults aged 50 –59 years at increased
risk of severe RSV disease?
▪Do the desirable effects outweigh the undesirable effects among adults aged 50 –59 years at
increased risk of severe RSV disease?Benefits and Harms GSK AREXVY vaccine in adults aged 50 –59 at
increased risk of severe RSV disease
Minimal Small Moderate Large Varies Don’t know
Minimal Small Moderate Large Varies Don’t know
Favors intervention (GSK AREXVY)
Favors comparison (no vaccine)
Favors both
Favors neither
Unclear
Majority opinion Minority opinion
95Evidence to Recommendations Framework
Summary: Work Group Interpretations
Yes NoAmong adults aged 50–59 years at increased risk of severe RSV disease :
Is there sufficient information to move forward with
a recommendation?
As of the June 26, 2024 ACIP meeting, the Work Group majority
has concluded there is currently insufficient evidence to make a
recommendation regarding RSV vaccination in adults 50 –59
years at today’s meeting.
96
Work Group Considerations on the use
of GSK AREXVY in adults 50 –59 years
at increased risk of severe RSV disease
97▪As demonstrated during the public health problem domain, the majority
of the Work Group felt that RSV -associated disease is or probably is a
public health problem among adults aged 50 -59 years at increased risk of
severe RSV disease.
▪This opinion is NOT a recommendation against  the use of RSV vaccine in
adults aged 50 –59 years.
▪Rather, the Work Group believes more information is needed to make a
population -level policy recommendation. This represents an opinion that additional information is needed to
determine the best policy for RSV vaccination in adults aged 50 –59 years.
98▪Among adults aged 50 –59 years, in whom
the absolute rates of RSV -associated
disease are lower, the balance of risk and
benefits is more uncertain than among
older age groups.
▪The Work Group recognizes that p ostponing
a policy recommendation may mean some
adults aged 50 –59 years who might benefit
from RSV vaccination will not receive a dose
this fall.The decision to postpone making a recommendation is primarily driven by
uncertainty in the balance of estimated benefits of RSV vaccine and potential risk
of GBS, specifically among adults aged 50 –59 years
The Work Group will
continue active
deliberation on the best
policy recommendation in
this age group as more
data become available and
will bring a
recommendation for ACIP’s
consideration as soon as
the Work Group believes
there is sufficient evidence.
99▪At least one complete season of safety surveillance data.
–Depending on certainty of findings, additional data may be needed.
▪Immunobridging  data in adults with immune compromise.
–Clinical trials including adults with immune compromise are underway.
▪Data on duration of protection and immune response after re -
vaccination
–Work Group has expressed concern that to date there are no data showing re -
vaccination will restore protection if efficacy wanes over time.
–While restoration of protection with re -vaccination is likely, efficacy in GSK’s pivotal
phase III trial did not improve after re -vaccination at a 12 -month interval.
–GSK immunogenicity data at 12 - and 24 -month re -vaccination intervals have shown a
weaker humoral immune response, compared with the response after dose 1. Before making a recommendation for adults aged 50 –59 years the Work
Group would like to review additional data
100The Work Group recognizes equity is an important concern in the use of RSV
vaccines in adults aged 50 –59 years and they considered equity in their
deliberations.
101▪This includes adults aged 50 –59 years and pending licensure, use of RSV
vaccine in adults aged <50 years.
▪The Work Group will continue to review data available from clinical trials,
real -world vaccine effectiveness, and safety monitoring.
▪While the timeline of availability of sufficient safety and other data is
unknown for a recommendation in adults 50–59 the Work Group will
present to ACIP the status of their deliberations as soon as there are
updated considerations. The Work Group is committed to ongoing assessment of
RSV vaccination in adults
102
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.

103
Back -Up Slides
104Prevalence of ≥1 chronic medical condition among adults 75 and older is at least 45%  using a narrow
definition of chronic medical conditions* and may be as high as 71% when using a broad definition**
National Health and Nutrition Examination Survey (NHANES), 2015 –2018.
*Narrow definition , at least one of:
•Serious heart disease
•Diabetes with complication
•Chronic obstructive pulmonary disease
•Asthma
•Severe obesity (BMI ≥40 kg/m2)
•Liver condition
•Chronic kidney disease, stage 4 or 5
**Broad definition , as above, OR:
•Diabetes with or without  complication
•Chronic kidney disease, stage 3, 4, or 5
•Cancer or malignancy in past 2 years
BMI: body mass index
SOURCE: National Center for Health Statistics (NCHS), National Health and Nutrition Examination Survey (NHANES), 2015 –2018. All estimates are crude estimates with no age adjustment and age is age at interview. Error bars represent Korn and Graubard  95% confidence intervals. NHANES is representative of the civilian, non -institutionalized U.S. population. For “narrow”
definition: Severe obesity was defined as BMI ≥40 kg/m2. Diabetes with complication was defined as 1) having diabetes: self -reported diabetes, fasting plasma glucose ≥126 mg/dL, or he moglobin A1c ≥6.5%, AND 2) having one of the following complications of diabetes assessed within the survey: serious heart di sease as defined below, chronic kidney disease (stage 3, 4, or 5) defined
as estimated glomerular filtration rate (eGFR) ˂60 (stages 3 –5) further defined below, or having self -reported diabetes and having a doctor previously told them that diabetes a ffected their eyes or that they have retinopathy. Other complications of diabetes are not included in this definition. Seriou s heart disease was defined based on self -report as diagnosed congestive heart failure,
coronary heart disease, angina, or heart attack, or angina grades 1 or 2 determined by the Rose Angina Questionnaire. Asthma was  defined as self -reporting ever being diagnosed with asthma and still having asthma. Chronic kidney disease was defined as estim ated glomerular filtration rate (eGFR) ˂30 (stages 4 –5), and using a forward equation for adjustment of creatinine because of
methods changes. eGFR calculated using the 2021 CKD -EPI creatinine equation (https://www.nejm.org/doi/10.1056/NEJMoa2102953). Ur ine albumin is not included in this definition. Chronic obstructive pulmonary disease (COPD) was defined as self -reported diagno sed COPD, emphysema, or current chronic bronchitis. Liver condition was defined as self -reporting ever being
diagnosed with any kind of liver condition and still having any kind of liver condition. Having at least one of the above con ditions for the narrow definition was defined based on the seven (7) conditions listed. For “broad” definition: conditions were defined identically except diabetes was defined as self -reported diabetes, fasting plasma glucose ≥126 mg/dL, or hemoglobin A1c ≥6. 5%
without complication; chronic kidney disease was defined as estimated glomerular filtration rate (eGFR) ˂60 (stages 3,4, or 5); and cancer or malignancy in past 2 years was added. This was defined as self -reporting having "ever been told by a doctor or other health profession that you had cancer or a malignancy of any kind" and reporting age at diagnosis i n years as being within 2
years of current age in years. As participant age and age at diagnosis for cancer or malignancy are top -coded for ages 80 years and above, those who are aged 80 years and above and report having diagnosis at age 78 years or above are coded as having can cer or malignancy in the past 2 years; this results in an inflated estimate. Of those with any history of cancer or malignancy ag es
50–79 years, 18.6% had a diagnosis within the past 2 years. Of those with any history of cancer or malignancy ages 80 years and above, 36.0% had a diagnosis at ≥ age 78 years. Having at least one of the above conditions for the broad definition was defi ned  based on the eight (8) conditions listed. Among the fasting sample, ~94% had complete data for all reported medical
conditions, ~6% were missing data for one (1) medical condition, <1% were missing data for two (2) medical conditions, and no ne were missing data for three (3) or more medical conditions. Estimates of having ≥1 condition are weighted using fasting sampl e weight.  313945 435771
0102030405060708090100
50–59 years 60–74 years 75 years and olderPrevalence of at least one chronic
medical condition (%)
105Per 1 Million Vaccine Doses Administered to Adults Aged 60 –74 Years
Without  Select Chronic Medical Conditions4:
1. Range of outcomes avertable was calculated using published 95% confidence interval (outpatient only) and adjusted 95% confide nce interval of RSV -associated incidence of the outcome in RSV -NET
2. FDA self -controlled case series analysis, among CMS Medicare beneficiaries ≥65 with Parts A, B, and D coverage who did not have a GBS claim in the 365 days before vaccination. Analysis based on
diagnoses of GBS in inpatient claims data in risk interval (1 -42 days after RSV vaccination) compared to control interval (43 -90 days after RSV vaccination). GBS cases identified using ICD -10 diagnosis of
GBS in primary position of inpatient claims coding. Estimates adjusted for outcome -dependent observation time, positive predicti ve value of diagnostic codes in identifying chart -confirmed GBS cases, and
seasonality. Analysis includes patients with RSV vaccinations  only through October 8, 2023 to allow for 90 -day post -vaccination  observation and 90% or greater claims data completeness. Claims data
through April 6, 2024.
3. Although CMS data were limited to Medicare beneficiaries aged ≥65 years, results are extrapolated here to include adults aged  60-64 years.
4. Without chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney disease, an d severe obesity (body mass index ≥40 kg/m2)
5. Self -controlled case series analysis estimated attributable risk of 3 (95% CI: -3, 10) GBS cases. However, the range was truncat ed at zero for Benefit/Risk analyses.Estimated RSV -Associated Outcomes1 Preventable over 2 RSV Seasons  vs. potential cases of GBS
(positive predictive value -adjusted  attributable risk of GBS in FDA -CMS partnership data among adults
aged ≥65 years, 42 -day risk interval2,3)
40 70 500
 -  1,000  2,000  3,000  4,000  5,000  6,000  7,00040 60 400
 -  1,000  2,000  3,000  4,000  5,000  6,000  7,000Hospitalizations
ICU Admissions
DeathsAREXVY (GSK) ABRYSVO (Pfizer)
3 (range 0–10)5 attributable  cases of GBS 16 (range 3–29) attributable cases of GBS(20–70) (10–60)(30–110) (40–110)(200 –700) (200 –700)
106GSK AREXVY Pfizer ABRYSVO Moderna mRESVIA
10-pack of single -dose kits Supplied as single dose, or as a 5 -
pack of single -dose kitsSupplied as single dose pre -filled
syringe or 10 -pack
Reconstitution required: single
dose vial of lyophilized powder
(antigen component) + single dose
vial of liquid (adjuvant component) Reconstitution required: single
dose vial of lyophilized powder
(antigen component) + single dose
vial OR prefilled syringe with
sterile water diluentNo reconstitution required
Both components should be
refrigerated (2 to 8 °C) in original
container, protected from lightProduct should be refrigerated (2
to 8 °C) in original container,
protected from light Store frozen ( -40 to -15°C), may be
stored refrigerated (2 to 8 °C) for up
to 30 days prior to use, protected
from light
After reconstitution, the product
should be administered within 4
hours , otherwise discarded After reconstitution, the product
should be administered within 4
hours , otherwise discardedThe pre -filled syringes may be
stored at room temperature (8 to
25°C) for a total of 24 hours  after
removal from refrigerated
conditions, otherwise discardStorage & handling requirements “back -up slide not shown at meeting”
107Moderna thawing conditions and times “back -up slide not shown at meeting”
mRESVIA  Prescribing Information: https://www.fda.gov/media/179005/download

108
Back -Up Slides: GRADE
109Outcome Importance Data SourcesEffect Estimate,
Vaccine Efficacya (95% CI)Concerns in certainty
assessment
RSV Lower Respiratory Tract
Disease (LRTD)b,c Important Two Phase 3 randomized
controlled trials (RCT) in adults
≥60 years1,2
• Pfizer RCT: Mean efficacy
follow up through 16 months
post -vaccination per
participant (median 17)
• GSK RCT: Mean efficacy
follow up through 19 months
post -vaccination per
participant (median 23)69.4% (36.6, 85.3) None
Medically attended RSV LRTDb,dCritical 76.6% (58.5, 86.8) Indirectness (serious)e
Hospitalization for RSV
respiratory illnessf Critical 75.7% ( -12.5, 94.8)Indirectness (serious)e
Imprecision (serious)g
Severe RSV respiratory illness
requiring O2/respiratory supportfImportant 62.7% ( -88.7, 92.6)Inconsistency (serious)h
Indirectness (serious)e
Imprecision (serious)g
Death due to RSV respiratory
illnessf Important Zero events observed Unable to evaluateProtein subunit RSV vaccines in adults aged ≥75 years
Benefits: vaccine efficacy estimates “back -up slide not shown at meeting”
a) Calculated as (1 – Incidence Rate Ratio) in meta -analyses using data provided by manufacturers. Events were included if they occ urred >14 days post -vaccination.
b) Case definitions differed across RCTs. Pfizer RCT included co -primary outcomes of lower respiratory tract illness (LRTI) with ≥2 or ≥3 lower respiratory signs/symptoms . Data included are for 3 -symptom LRTI. GSK RCT
included a single primary outcome of LRTD.
c) Included data are from participants aged ≥75 years.
d) Included data are from Pfizer RCT participants aged ≥75 years, and among all GSK RCT participants (aged ≥60 years).
e) Serious concern for indirectness due to inclusion of adults aged 60 –74 years.
f) Included data are from all participants (aged ≥60 years) from both RCTs. Data from GSK include only a mean follow up time of 15 months per participant (median 18 months).
g) Serious concern for imprecision due to the confidence intervals containing absolute risk reduction estimates for which differ ent policy decisions might be considered.
h) Serious concern for inconsistency because the point estimates between the studies differed substantially, although the confid ence intervals overlapped
1. Papi  A, et al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. NEJM 2023; 388:595 –608 https://doi.org/10.1056/NEJMoa2209604  and Ison MG, Papi  A, Athan  E, et al. Efficacy and Safety of
Respiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine (RSVPreF3 OA) in Older Adults Over 2 RSV Seasons. CID. 2024; on line ahead of print https://doi.org/10.1093/cid/ciae010   plus additional data obtained
directly from the manufacturer
2. Walsh EE, et al. Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults. NEJM 2023. 388(16): 1465 -1477. https://doi.org/10.1056/NEJMoa2213836  plus additional data obtained directly from the
manufacturer
110Protein subunit RSV vaccines in adults aged ≥75 years
Harms “back -up slide not shown at meeting”
a) Pooled relative risk estimates were calculated in meta -analyses using data provided by manufacturers.
b) Included data are from all participants from all trials (aged ≥60 years).
c) Within 6 months after vaccination
d) Serious concern for indirectness due to inclusion of adults aged 60 –74 years.
e) Within 42 days after vaccination
f) Very serious concern for imprecision due to the width of the confidence interval containing estimates for which different pol icy decisions might be considered and fragility in the estimate.
g) Pfizer RCTs: within 7 days after vaccination. GSK phase 3 RCT: within 4 days after vaccination. GSK phase 1/2 RCT: within 7 d ays after vaccination.
h) Inconsistency noted due to I2 value of observed trial outcomes 58%, but this was expected due to differing reactogenicity results for each vaccine observed  in post -licensure data.
i) Serious concern for imprecision due to the width of the confidence interval containing estimates for which different policy de cisions might be considered
1. Papi  A, Ison MG, Langley JM, et al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. NEJM. 2023; 388:595 –608 https://doi.org/10.1056/NEJMoa2209604  plus additional data
obtained directly from the manufacturer
2. Walsh EE, Pérez Marc G, Zareba AM, et al. Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults. 2023. 38 8(16): 1465 -1477. https://doi.org/10.1056/NEJMoa2213836  plus
additional data obtained directly from the manufacturer
3. Leroux -Roels  I, David MG, Steenackers  K, et al. Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F (RSVPreF3) Candidate Vaccine in Older Adults : Phase 1/2 Randomized Clinical
Trial, The Journal of Infectious Diseases, Volume 227, Issue 6, 15 March 2023, Pages 761 –772, https://doi.org/10.1093/infdis/jiac327  plus additional data obtained directly from the manufacturer
4. Falsey  AR, Walsh EE, Scott DA, et al. Phase 1/2 Randomized Study of the Immunogenicity, Safety, and Tolerability of a Respiratory Sy ncytial Virus Prefusion F Vaccine in Adults with Concomitant
Inactivated Influenza Vaccine. The Journal of Infectious Diseases. 225(12): 2056 -2066. https://doi.org/10.1093/infdis/jiab611   plus additional data obtained directly from the manufacturerOutcome Importance Data SourcesEffect Estimate,
Relative riska (95% CI)Concerns in certainty assessment
Serious adverse events
(SAEs)b,c Critical
Two phase 3 RCTs1,2
Two phase 1/2 RCTs3,41.01 (0.93, 1.10) Indirectness (serious)d
Inflammatory
neurologic eventsb,e Critical 1.76 (0.29, 10.77)Indirectness (serious)d
Imprecision (very serious)f
Reactogenicity (grade
≥3)b,g Important 1.92 (0.78, 4.70)Indirectness (serious)d
Inconsistency (not serious)h
Imprecision (serious)i
111Outcome Importance Data SourcesEffect Estimate,
Vaccine Efficacya (95% CI)Concerns in certainty
assessment
RSV Lower Respiratory Tract Disease
(L TRD)b,c ImportantTwo phase 3 randomized
controlled trials (RCT) in adults
≥60 years1,2
• Pfizer RCT: Mean efficacy
follow up through 16 months
post -vaccination per
participant (median 17)
• GSK RCT: Mean efficacy
follow up through 19 months
post -vaccination per
participant (median 23)73.1% (58.7, 82.4) None
Medically attended RSV LRTDb,cCritical 72.7% (52.9, 84.2) None
Hospitalization for RSV respiratory
illnessd Critical 75.7% ( -12.5, 94.8)Indirectness (serious)e
Imprecision (serious)f
Severe RSV respiratory illness
requiring O2/respiratory supportd Important 62.7% ( -88.7, 92.6)Indirectness (serious)e
Imprecision (serious)f
Inconsistency (serious)g
Death due to RSV respiratory illnessdImportant Zero events observed Unable to evaluateRSV protein subunit vaccines in adults aged 60 –74 years at increased risk of severe RSV disease
Benefits: vaccine efficacy estimates “back -up slide not shown at meeting”
a) Calculated as (1 – Incidence Rate Ratio) in meta -analyses using data provided by manufacturers. Events were included if they occ urred >14 days post -vaccination.
b) Case definitions differed across RCTs. Pfizer RCT included co -primary outcomes of lower respiratory tract illness (LRTI) with ≥2 or ≥3 lower respiratory signs/symptoms . Data included are for 3 -symptom LRTI.
GSK RCT included a single primary outcome of LRTD.
c) Included data are from participants aged 60 –74 years with ≥1 comorbidity (GSK: Pre -existing comorbidities of interest includes C OPD, Asthma, Any chronic respiratory/pulmonary disease, Chronic heart failure,
Diabetes mellitus Type 1 or Type 2, Advanced liver or renal disease) (Pfizer: Current tobacco use, diabetes, lung disease [in cluding COPD], heart disease [including congestive heart failure], liver disease, renal
disease)
d) Included data are from all participants (aged ≥60 years) from both RCTs. Data from GSK include only a mean follow up time of 15 months per participant (median 18 months).
e) Serious concern for indirectness due to inclusion of adults without chronic medical conditions.
f) Serious concern for imprecision due to the confidence intervals containing absolute risk reduction estimates for which differ ent policy decisions might be considered.
g) Serious concern for inconsistency because the point estimates between the studies differed substantially, although the confid ence intervals overlapped
1. Papi  A, et al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. NEJM 2023; 388:595 –608 https://doi.org/10.1056/NEJMoa2209604  and Ison MG, Papi  A, Athan  E, et al. Efficacy and Safety of
Respiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine (RSVPreF3 OA) in Older Adults Over 2 RSV Seasons. CID. 2024; on line ahead of print https://doi.org/10.1093/cid/ciae010   plus additional data obtained
directly from the manufacturer
2. Walsh EE, et al. Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults. NEJM 2023. 388(16): 1465 -1477. https://doi.org/10.1056/NEJMoa2213836  plus additional data obtained directly from
the manufacturer
112a) Pooled relative risk estimates were calculated in meta -analyses using data provided by manufacturers.
b) Included data are from all participants (aged ≥60 years).
c) Within 6 months after vaccination
d) Serious concern for indirectness due to inclusion of adults aged 60 –74 years.
e) Within 42 days after vaccination
f) Very serious concern for imprecision due to the width of the confidence interval containing estimates for which different pol icy decisions might be considered and fragility in the estimate.
g) Pfizer RCTs: within 7 days after vaccination. GSK phase 3 RCT: within 4 days after vaccination. GSK phase 1/2 RCT: within 7 d ays after vaccination.
h) Serious concern for imprecision due to the width of the confidence interval containing estimates for which different policy d ecisions might be considered.
i) Inconsistency noted due to I2 value of observed trial outcomes 58%, but this was expected due to differing reactogenicity results for each vaccine observed  in post -licensure data.
1. Papi  A, et al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. NEJM 2023; 388:595 –608 https://doi.org/10.1056/NEJMoa2209604  and Ison MG, Papi  A, Athan  E, et al.
Efficacy and Safety of Respiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine (RSVPreF3 OA) in Older Adults Over 2 RSV  Seasons. CID. 2024; online ahead of print
https://doi.org/10.1093/cid/ciae010   plus additional data obtained directly from the manufacturer
2. Walsh EE, Pérez Marc G, Zareba AM, et al. Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults. 2023. 38 8(16): 1465 -1477. https://doi.org/10.1056/NEJMoa2213836  plus
additional data obtained directly from the manufacturer
3. Leroux -Roels  I, David MG, Steenackers  K, et al. Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F (RSVPreF3) Candidate Vaccine in Older Adults : Phase 1/2 Randomized
Clinical Trial, The Journal of Infectious Diseases, Volume 227, Issue 6, 15 March 2023, Pages 761 –772, https://doi.org/10.1093/infdis/jiac327  plus additional data obtained directly from the
manufacturer
4. Falsey  AR, Walsh EE, Scott DA, et al. Phase 1/2 Randomized Study of the Immunogenicity, Safety, and Tolerability of a Respiratory Sy ncytial Virus Prefusion F Vaccine in Adults with Concomitant
Inactivated Influenza Vaccine. The Journal of Infectious Diseases. 225(12): 2056 -2066. https://doi.org/10.1093/infdis/jiab611   plus additional data obtained directly from the manufacturerOutcome Importance Data SourcesEffect Estimate, Relative Risk
(95% CI)aConcerns in certainty
assessment
Serious adverse
events (SAEs)b,cCriticalTwo phase 3 RCT1,2
two phase 1/2 RCT3,4 1.01 (0.93, 1.10) Indirectness (serious)d
Inflammatory
neurologic eventsb,eCriticalTwo phase 3 RCT1,2
two phase 1/2 RCT3,4 1.76 (0.29, 10.77)Indirectness (serious)d
Imprecision (very serious)f
Reactogenicity
(grade ≥3)b,gImportantTwo phase 3 RCT1,2
two phase 1/2 RCT3,4 1.92 (0.78, 4.70)Indirectness (serious)d
Imprecision (serious)h
Inconsistency (not serious)iRSV protein subunit vaccines in adults aged 60 –74 years at increased risk of severe RSV disease
Harms “back -up slide not shown at meeting”
113Outcome Importance Data SourcesEffect Estimate,
Geometric mean titer ratioEffect estimate,
efficacya (95% CI)
in adults aged ≥60 yearsConcerns in certainty
assessment
RSV Lower Respiratory
Tract Disease (L TRD)Important
One phase 3
RCT in adults
aged 50 –59
and ≥60 years1
One phase 3
RCT in adults
aged ≥60
years2Adults 50 –59 at increased risk
vs. adults ≥60:
RSV -A: 1.20 (95% CI: 1.05, 1.37)b
RSV -B: 1.25 (95% CI: 1.10, 1.41)b73.3% (60.7, 82.3)
Assessed using mean 19 mo. follow upIndirectness (serious)c
Medically attended RSV
LRTDCritical 77.6% (58.3, 88.9)
Assessed using mean 19 mo. follow upIndirectness (serious)c
Hospitalization for RSV
respiratory illnessCritical 76.4% ( -102.3, 97.2)
Assessed using mean 15 mo. follow upIndirectness (serious)c
Imprecision (very serious)d
Severe RSV respiratory
illness requiring
O2/respiratory supportImportant76.4% ( -102.3, 97.2)
Assessed using mean 15 mo. follow upIndirectness (serious)c
Imprecision (very serious)d
Death due to RSV
respiratory illnessImportant Zero events observed Unable to evaluate
a) Calculated as (1 – Incidence Rate Ratio) using data provided by manufacturer. Events were included if they occurred >14 days pos t-vaccination.
b) Titers assessed through neutralization assay on Day 31, where Day 1 was day of vaccination.
c) Serious concern for indirectness as the outcome was evaluated using immunobridging  data as a surrogate for vaccine efficacy and there is no established  correlate of protection
d) Very serious concern for imprecision due to the vaccine efficacy estimate confidence interval in adults 60 and older containi ng estimates for which different policy decisions might be considered, and
for fragility of the estimate.
1. https://clinicaltrials.gov/study/NCT05590403 , https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -10-25-26/02 -gerber -adult -RSV -508.pdf , unpublished data provided by manufacturer
2. Papi  A, et al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. NEJM 2023; 388:595 –608 https://doi.org/10.1056/NEJMoa2209604 , Ison MG, Papi  A, Athan  E, et al. Efficacy and
Safety of Respiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine (RSVPreF3 OA) in Older Adults Over 2 RSV Seasons. CID . 2024; online ahead of print https://doi.org/10.1093/cid/ciae010  ,
additional data obtained directly from the manufacturerGSK AREXVY vaccine in adults aged 50 –59 years at increased risk of severe RSV disease
Benefits: immunobridging “back -up slide not shown at meeting”
114a) Within 6 months after vaccination
b) Serious concern for impression due to the width of the confidence interval containing estimates for which different policy de cisions might be
considered
c) Serious concern for indirectness due to inclusion of adults without chronic conditions that increase the risk of severe RSV d isease.
d) Within 42 days after vaccination
e) Within 4 days after vaccination
1.https://clinicaltrials.gov/study/NCT05590403 , https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -10-25-26/02 -
gerber -adult -RSV -508.pdf , unpublished data provided by manufacturerOutcome Importance Data SourcesEffect Estimate,
relative risk (95% CI)Concerns in certainty
assessment
Serious adverse events (SAEs)a Critical
One phase 3 RCT11.12 (0.43, 2.55)Imprecision (serious)b
Indirectness (serious)c
Inflammatory neurologic eventsd Critical Zero events observed Unable to evaluate
Reactogenicity (grade ≥3)e Important 2.81 (1.45, 5.45) Indirectness (serious)cGSK AREXVY vaccine in adults aged 50 –59 years at increased risk of severe RSV disease
Harms “back -up slide not shown at meeting”

Summary: 1 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. Evidence to Recommendations Framework (EtR): RSV Vaccination in Adults Aged 50 –59 years, 60 –74 years,  and 75 years and older Amadea Britton, MD, Co -Lead Adult RSV…