Centers for Disease Control and Prevention

Evidence to Recommendations Framework

Respiratory Syncytial Virus (RSV) in Adults

Pfizer bivalent RSVpreF vaccine in older adults 

GSK adjuvanted RSVPreF3 vaccine in older adults

Michael Melgar, MD

Amadea Britton, MD

Advisory Committee on Immunization Practices

June 21, 2023
2

Evidence to Recommendations (EtR) Framework

Policy Questions

▪ Should a single dose of Pfizer bivalent RSVpreF vaccine (120μg antigen, 1 dose IM), 

rather than no vaccine, be recommended in persons aged ≥65 years?

▪ Should a single dose of Pfizer bivalent RSVpreF vaccine (120μg antigen, 1 dose IM), 

rather than no vaccine, be recommended in persons aged 60–64 years?

▪ Should a single dose of GSK RSVPreF3 vaccine (120μg antigen + AS01Eadjuvant, 1 

dose IM), rather than no vaccine, be recommended in persons aged ≥65 years?

▪ Should a single dose of GSK RSVPreF3 vaccine (120μg antigen + AS01Eadjuvant, 1 

dose IM), rather than no vaccine, be recommended in persons aged 60–64 years?
3

Evidence to Recommendations (EtR) Framework

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 variability in how patients value the outcome?

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 in the impact of the intervention on health equity?
4

Evidence to Recommendations (EtR) Framework

EtR Domain

Public Health Problem

Benefits and Harms

Values

Acceptability

Feasibility

Resource Use

Equity
5

Evidence to Recommendations (EtR) Framework

Manufacturer-specific data will be presented

EtR Domain

Public Health Problem

Benefits and Harms

Values

Acceptability

Feasibility

Resource Use

Equity
6

Evidence to Recommendations (EtR) Framework

Use of RSV vaccines broadly will be presented

EtR Domain

Public Health Problem

Benefits and Harms

Values

Acceptability

Feasibility

Resource Use

Equity
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?
8

Benefits and Harms

▪ Pfizer bivalent RSVpreF vaccine 

– Grading of Recommendations, Assessment, Development and 

Evaluation (GRADE) Summary

– Modeling potential number of RSV-attributable illnesses prevented

▪ GSK adjuvanted RSVPreF3 vaccine

– GRADE Summary

– Modeling potential number of RSV-attributable illnesses prevented
9

GRADE Framework: PICO Question

▪

Population Persons aged ≥60 years

Intervention Pfizer bivalent RSVpreF vaccine (120μg antigen, 1 dose IM) 

-orGSK RSVPreF3 vaccine (120 μg antigen + AS01E

adjuvant, 1 dose IM)

Comparison No RSV vaccine

Outcomes ▪ RSV lower respiratory tract illness/disease (LRTI/LRTD)

▪ Medically attended RSV LRTI/LRTD

▪ Hospitalization for RSV respiratory illness

▪ Severe RSV respiratory illness requiring supplemental O2 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)
10

GRADE Framework: PICO Question

▪

Population Persons aged ≥60 years

Intervention Pfizer bivalent RSVpreF vaccine (120μg antigen, 1 dose IM) 

-orGSK RSVPreF3 vaccine (120 μg antigen + AS01E

adjuvant, 1 dose IM)

Comparison No RSV vaccine

Outcomes ▪ RSV lower respiratory tract illness/disease (LRTI/LRTD)

▪ Medically attended RSV LRTI/LRTD

▪ Hospitalization for RSV respiratory illness

▪ Severe RSV respiratory illness requiring supplemental O2 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)
11

Case definitions of lower respiratory tract 

illness/disease were not aligned across clinical trials

▪ Pfizer

▪ RSV LRTI with ≥2 lower respiratory 

signs/symptoms (co-primary outcome)

▪ RSV LRTI with ≥3 lower respiratory 

signs/symptoms (co-primary outcome)

▪ Lower respiratory signs/symptoms:

– Sputum, cough, shortness of breath, 

wheezing, tachypnea

▪ GSK

▪ RSV LRTD (primary outcome)

– ≥2 lower respiratory symptoms or 

signs, including ≥1 sign, OR

– ≥3 lower respiratory symptoms

▪ Lower respiratory symptoms:

– Sputum, cough, dyspnea

▪ Lower respiratory signs:

– Wheezing, crackles/rhonchi, 

tachypnea, hypoxemia, O2

supplementation
12

Case definitions of lower respiratory tract 

illness/disease were not aligned across clinical trials

▪ Pfizer

▪ RSV LRTI with ≥2 lower respiratory 

signs/symptoms (co-primary outcome)

▪ RSV LRTI with ≥3 lower respiratory 

signs/symptoms (co-primary outcome)

▪ Lower respiratory signs/symptoms:

– Sputum, cough, shortness of breath, 

wheezing, tachypnea

▪ GSK

▪ RSV LRTD (primary outcome)

– ≥2 lower respiratory symptoms or 

signs, including ≥1 sign, OR

– ≥3 lower respiratory symptoms

▪ Lower respiratory symptoms:

– Sputum, cough, dyspnea

▪ Lower respiratory signs:

– Wheezing, crackles/rhonchi, 

tachypnea, hypoxemia, O2

supplementation
13

GRADE: Pfizer bivalent RSVpreF
14

Pfizer, Benefits: vaccine efficacy estimates

OutcomeImportance Data sources Vaccine efficacy (%)a

(95% confidence interval)

Concerns in certainty 

assessment

Benefits

RSV Lower Respiratory Tract Illness 

(LRTI)b

Critical

One phase 3 RCTc,

- 10.6 months mean 

follow up time 

under surveillance, 

including partial 

season 2d

- 31,986 personyears under 

surveillance

84.4 (59.6, 95.2)

Vaccine: n=5, Placebo: n=32 Indirectness (serious)e

Medically attended RSV LRTIb Critical 81.0 (43.5, 95.2)

Vaccine: n=4, Placebo: n=21 Indirectness (serious)e

Hospitalization for RSV respiratory 

illness Important 66.7 (-315, 99.4)

Vaccine: n=1, Placebo: n=3

Indirectness (serious)e

Imprecision (very 

serious)f

Severe RSV respiratory illness 

requiring O2/respiratory support Important 0 (-7750, 98.7)

Vaccine: n=1, Placebo: n=1

Indirectness (serious)e

Imprecision (very 

serious)f

Death due to RSV respiratory illness Important Vaccine: n=0/16,010 person-years

Placebo: n=0/15,976 person-years

Unable to evaluateg

a Efficacy estimates were independently calculated using counts of events and total person-time available from the Pfizer pivotal phase 3 trial. Data provided by manufacturer. 

Efficacy was calculated as 1 – incidence rate ratio. Events of each outcome were included if they occurred on or after day 15 after injection. Manufacturer used the same 

methodology to calculate efficacy estimates.

b Pfizer pivotal phase 3 trial included co-primary outcomes of LRTI with ≥2 lower respiratory signs or symptoms, and LRTI with ≥3 lower respiratory signs or symptoms. In GRADE, 

the outcome of LRTI with ≥3 lower respiratory signs or symptoms was used.

c RCT = randomized controlled trial. Walsh EE, et al. Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults. 2023. NEJM. https://doi.org/10.1056/nejmoa2213836

d Mean time from vaccination to end of efficacy follow up, including a gap in RSV surveillance, was 12 months per participant. Among participants who contributed to partial 

Season 2, this was 13.9 months per participant.

e Underrepresentation of adults aged ≥75 years and adults with congestive heart failure. Exclusion of adults with immune compromise.

f 95% confidence interval for measure of absolute risk included potential for both benefit and harm. Fragility of estimates.

g No RSV-associated deaths were recorded.
15

Pfizer, Benefits: vaccine efficacy estimates

OutcomeImportance Data sources Vaccine efficacy (%)a

(95% confidence interval)

Concerns in certainty 

assessment

Benefits

RSV Lower Respiratory Tract Illness 

(LRTI)b

Critical

One phase 3 RCTc,

- 10.6 months mean 

follow up time 

under surveillance, 

including partial 

season 2d

- 31,986 personyears under 

surveillance

84.4 (59.6, 95.2)

Vaccine: n=5, Placebo: n=32 Indirectness (serious)e

Medically attended RSV LRTIb Critical 81.0 (43.5, 95.2)

Vaccine: n=4, Placebo: n=21 Indirectness (serious)e

Hospitalization for RSV respiratory 

illness Important 66.7 (-315, 99.4)

Vaccine: n=1, Placebo: n=3

Indirectness (serious)e

Imprecision (very 

serious)f

Severe RSV respiratory illness 

requiring O2/respiratory support Important 0 (-7750, 98.7)

Vaccine: n=1, Placebo: n=1

Indirectness (serious)e

Imprecision (very 

serious)f

Death due to RSV respiratory illness Important Vaccine: n=0/16,010 person-years

Placebo: n=0/15,976 person-years

Unable to evaluateg

a Efficacy estimates were independently calculated using counts of events and total person-time available from the Pfizer pivotal phase 3 trial. Data provided by manufacturer. 

Efficacy was calculated as 1 – incidence rate ratio. Events of each outcome were included if they occurred on or after day 15 after injection. Manufacturer used the same 

methodology to calculate efficacy estimates.

b Pfizer pivotal phase 3 trial included co-primary outcomes of LRTI with ≥2 lower respiratory signs or symptoms, and LRTI with ≥3 lower respiratory signs or symptoms. In GRADE, 

the outcome of LRTI with ≥3 lower respiratory signs or symptoms was used.

c RCT = randomized controlled trial. Walsh EE, et al. Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults. 2023. NEJM. https://doi.org/10.1056/nejmoa2213836

d Mean time from vaccination to end of efficacy follow up, including a gap in RSV surveillance, was 12 months per participant. Among participants who contributed to partial 

Season 2, this was 13.9 months per participant.

e Underrepresentation of adults aged ≥75 years and adults with congestive heart failure. Exclusion of adults with immune compromise.

f 95% confidence interval for measure of absolute risk included potential for both benefit and harm. Fragility of estimates.

g No RSV-associated deaths were recorded.
16

Pfizer: RSV lower respiratory tract illness (LRTI), 

defined by ≥3 lower respiratory signs or symptoms

Population Case split 

(vaccine/placebo)a

Manufacturer-calculated 

vaccine efficacy, % (95% CI)

All (age ≥60 years) 5/32 84.4 (59.6, 95.2)

Age ≥65 years 3/23 87.0 (56.8, 97.5)

Age ≥70 years 1/11 90.9 (37.5, 99.8)

Age ≥75 years 1/7 85.7 (-11.2, 99.7)b

Age ≥80 years 0/4 100.0 (-51.5, 100.0)b

a Pfizer pivotal phase 3 trial (Walsh EE, et al. NEJM 2023 https://doi.org/10.1056/nejmoa2213836). Events of each 

outcome were included if they occurred on or after day 15 after injection. Average time, across participants, from 

vaccination to end of efficacy follow up was 12 months, including unpublished data provided by manufacturer from 

partial season 2. Total 36,127 participants (31,986 person-years) under surveillance.

b Highlighted text indicates that evidence of statistically significant efficacy is lacking.
17

Population Case split 

(vaccine/placebo)a

Manufacturer-calculated 

vaccine efficacy, % (95% CI)

≥1 pre-existing comorbidity of 

interestb 4/20 80.0 (40.3, 95.0)

≥1 pre-existing cardiorespiratory 

comorbidityc 3/11 72.7 (-3.2, 95.1)d

Adults who are frail Not assessedd

a Pfizer pivotal phase 3 trial (Walsh EE, et al. NEJM 2023 https://doi.org/10.1056/nejmoa2213836). Events of each outcome were 

included if they occurred on or after day 15 after injection. Average time, across participants, from vaccination to end of efficacy 

follow up was 12 months, including unpublished data provided by manufacturer from partial season 2. Total 36,127 participants

(31,986 person-years) under surveillance.

b COPD, asthma, diabetes mellitus, congestive heart failure, liver or renal disease

c COPD, asthma, congestive heart failure

d Highlighted text indicates that evidence of statistically significant efficacy is lacking.

Pfizer: RSV lower respiratory tract illness (LRTI), 

defined by ≥3 lower respiratory signs or symptoms
18

Pfizer, Harms: relative risk

OutcomeImportance Data sources Relative risk estimatea

(95% confidence interval)

Concerns in certainty 

assessment

Harms

Serious adverse events 

(SAEs) Critical One phase 3 RCT,

one phase 1/2 RCTb

1.04 (0.94, 1.15)

N=36,953 total participants None serious

Inflammatory neurologic 

events

Important One phase 3 RCTc

one phase 1/2 RCTc

Vaccine: n=3/18,622 participantsd

Placebo: n=0/18,335 participantse

Imprecision

(very serious)f,g

Reactogenicity (grade ≥3) Important One phase 3 RCTh

one phase 1/2 RCTh

1.43 (0.85, 2.39)

N=7,164 total participants

Imprecision

(serious)f

a Pooled relative risk estimates were independently calculated using counts of events and participants in the Pfizer pivotal phase 3 trial (Walsh EE et 

al. NEJM 2023 https://doi.org/10.1056/nejmoa2213836), as well as from a placebo-controlled phase 1/2 dosing selection study (Falsey AR, et al. J 

Infect Dis. 2022 https://doi.org/10.1093/infdis/jiab611). Data provided by manufacturer.

b After dose 1, but before dose 2 (day 61). RCT = randomized controlled trial.

c Within 42 days after injection. RCT = randomized controlled trial.

d

In the Pfizer pivotal phase 3 trial, 2 events of Guillain-Barré syndrome (GBS) and 1 event of motor-sensory axonal polyneuropathy were reported 

within 42 days after vaccination with RSVpreF, compared with zero in the placebo arm. One additional case of GBS was reported 8 months after 

vaccination with RSVpreF and one additional case of GBS was reported 14 months after placebo receipt. No events were recorded in the phase 1/2 

formulation selection study.

e Measures of relative and absolute risk were not calculated due to zero events within 42 days in placebo recipients.

f 95% confidence interval for measure of absolute risk included potential for both benefit and harm.

g Fragility of estimate.

h Within 7 days after vaccination. RCT = randomized controlled trial.
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a Pooled relative risk estimates were independently calculated using counts of events and participants in the Pfizer pivotal phase 3 trial (Walsh EE et 

al. NEJM 2023 https://doi.org/10.1056/nejmoa2213836), as well as from a placebo-controlled phase 1/2 dosing selection study (Falsey AR, et al. J 

Infect Dis. 2022 https://doi.org/10.1093/infdis/jiab611). Data provided by manufacturer.

b After dose 1, but before dose 2 (day 61). RCT = randomized controlled trial.

c Within 42 days after injection. RCT = randomized controlled trial.

d

In the Pfizer pivotal phase 3 trial, 2 events of Guillain-Barré syndrome (GBS) and 1 event of motor-sensory axonal polyneuropathy were reported 

within 42 days after vaccination with RSVpreF, compared with zero in the placebo arm. One additional case of GBS was reported 8 months after 

vaccination with RSVpreF and one additional case of GBS was reported 14 months after placebo receipt. No events were recorded in the phase 1/2 

formulation selection study.

e Measures of relative and absolute risk were not calculated due to zero events within 42 days in placebo recipients.

f 95% confidence interval for measure of absolute risk included potential for both benefit and harm.

g Fragility of estimate.

h Within 7 days after vaccination. RCT = randomized controlled trial.

Pfizer, Harms: relative risk

OutcomeImportance Data sources Relative risk estimatea

(95% confidence interval)

Concerns in certainty 

assessment

Harms

Serious adverse events 

(SAEs) Critical One phase 3 RCT,

one phase 1/2 RCTb

1.04 (0.94, 1.15)

N=36,953 total participants None serious

Inflammatory neurologic 

events

Important One phase 3 RCTc

one phase 1/2 RCTc

Vaccine: n=3/18,622 participantsd

Placebo: n=0/18,335 participantse

Imprecision

(very serious)f,g

Reactogenicity (grade ≥3) Important One phase 3 RCTh

one phase 1/2 RCTh

1.43 (0.85, 2.39)

N=7,164 total participants

Imprecision

(serious)f

Total of 3 inflammatory neurologic events reported 

within 42 days of vaccination with RSVpreF among 

20,255 older adults across all clinical trials
20

Pfizer: Total inflammatory neurologic events reported within 42 

days of vaccination across all clinical trials

Participant 

age

Country Reported as Onset Trial Work group case 

review

66 years United 

States

GBSa, Brighton 

Collaborationblevel 1

14 days postvaccinationPivotal phase 3 trial, 

randomized, blinded, placebocontrolled

Clinical course more 

consistent with CIDPc

66 years Japan GBSa, Miller-Fisher 

variant, Brighton 

Collaborationblevel 4

10 days postvaccinationPivotal phase 3 trial, 

randomized, blinded, placebocontrolled

Possible GBS (Miller 

Fisher syndrome) 

though other causes 

are also possible

68 years Argentina Motor-sensory 

axonal 

polyneuropathy*

*Site investigator reported 

as not associated with 

vaccination

21 days postvaccination*

*Participant 

reported some 

symptoms preceded 

vaccination

Pivotal phase 3 trial, 

randomized, blinded, placebocontrolled

Undifferentiated 

motor-sensory axonal 

polyneuropathy

a GBS = Guillain Barre syndrome

b https://brightoncollaboration.us/guillain-barre-and-miller-fisher-syndromes-case-definition-companion-guide/

c CIDP = chronic inflammatory demyelinating polyneuropathy
21

Background incidence of Guillain-Barré syndrome 

among older adults 

a Sejvar JJ, et al. Population incidence of Guillain-Barré syndrome: a systematic review and meta-analysis. Neuroepidemiology. 2011;36(2):123-33. https://doi.org/10.1159/000324710

b Shui IM, et al. Guillain-Barré syndrome incidence in a large United States cohort (2000-2009). Neuroepidemiology. 2012;39(2):109-15. https://doi.org/10.1159/000339248

Age group, 

years

Annual rate per 100,000 

population (95% CI)

0–9 0.62 (0.52–0.75)

10–19 0.75 (0.60–0.92)

20–29 0.90 (0.67–1.19)

30–39 1.07 (0.74–1.56)

40–49 1.29 (0.80–2.06)

50–59 1.54 (0.87–2.74)

60–69 1.85 (0.94–3.64)

70–79 2.22 (1.01–4.86)

80–89 2.66 (1.09–6.48)

Meta-analysisa, 13 studies, North America & Europe

Age group, 

years

Annual rate per 100,000 population

(95% CI)

Female Male

0–4 0.51 (0.24–0.78) 0.39 (0.16–0.61)

5–17 0.43 (0.29–0.57) 0.62 (0.46–0.79)

18–24 0.64 (0.39–0.89) 0.75 (0.47–1.03)

25–49 1.00 (0.85–1.15) 1.39 (1.20–1.57)

50–64 2.19 (1.90–2.50) 2.85 (2.49–3.21)

≥65 4.68 (4.14–5.21) 7.06 (6.31–7.81)

Vaccine Safety Datalink, United States, 2000–2009b
22

Estimated incidence of Guillain-Barre syndrome (GBS) following other 

recommended vaccinations

▪ Seasonal influenza vaccinesa: The data on the association between GBS and 

seasonal flu vaccination are variable and inconsistent across flu seasons. If there is 

an increased risk of GBS following flu vaccination it is small, on the order of 1–2 

additional cases per million doses of flu vaccine administered.

▪ Recombinant zoster vaccineb: 3 excess cases per million doses administered

– 6 excess cases per million first doses administered, no increased risk following 

the second dose

a https://www.cdc.gov/flu/prevent/guillainbarre.htm#how1

b https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-requires-warning-about-guillain-barre-syndrome-gbs-be-included-prescribing-informationshingrix
23

Summary of GRADE for Pfizer RSVpreF vaccine in older adults

OutcomeImportance Design

(# of studies)

FindingsEvidence

type

Benefits

RSV Lower Respiratory Tract 

Disease (LTRI) Critical RCT (1) Pfizer RSVpreF likely reduces RSV LRTI. Moderate

Medically attended RSV LRTI Critical RCT (1) Pfizer RSVpreF likely reduces medically attended RSV LRTI. Moderate

Hospitalization for RSV 

respiratory illness Important RCT (1) Pfizer RSVpreF may reduce hospitalization for RSV respiratory illness, but the effect is very uncertain. Very low

Severe RSV respiratory 

illness requiring 

O2/respiratory support

Important RCT (1)

Pfizer RSVpreF may not impact severe RSV respiratory illness 

requiring supplemental oxygen or other respiratory support, but 

the effect is very uncertain.

Very low

Death due to RSV respiratory 

illness Important RCT (1) No events observed Unable to evaluate

Harms

Serious adverse eventsCritical RCT (2) Pfizer RSVpreF results in little to no differences in SAEs. High

Inflammatory neurologic 

events

Important RCT (2) Pfizer RSVpreF may increase inflammatory neurologic events. Low

Reactogenicity (grade ≥3) Important RCT (2) Pfizer RSVpreF likely increases severe reactogenicity events. Moderate
24

Summary of GRADE for Pfizer RSVpreF vaccine in older adults

Overall evidence rating: Moderate certainty
25

RSV-NET estimated annual hospitalizations per 

100,000 adults: 2016–2017 to 2019–2020

0

50

100

150

200

250

300

350

400

450

18-49 yrs 50-59 yrs 60-64 yrs ≥65 yrs 65-69 yrs 70-74 yrs ≥75 yrs

Annual RSV-associated hospitalizations 

per 100,000 population

2016-17

2017-18

2018-19

2019-20

CDC RSV-NET unpublished data. Estimates are adjusted for under-testing and incomplete test sensitivity. https://www.cdc.gov/rsv/research/rsv-net/index.html
26

Modeling potential RSV-attributable illnesses prevented:

Pfizer RSVpreF

▪ Included in economic analysis performed by U. Michigan, using published incidence 

estimates and RSV-NET estimated annual hospitalizations per 100,000 adults

▪ Timeframe: 2 RSV seasons (assumed duration of vaccine protection)

Number prevented per 1 

million vaccinations among:

Adults aged ≥65 years

Number prevented per 1 

million vaccinations among:

Adults aged 60–64 years

Outpatient visitsa 25,000 19,000

Hospitalizationsb 2,500 960

Deathsc 130 37

a

Incidence rates of RSV illness requiring outpatient visit taken from McLaughlin et al, OFID (2022). Vaccine efficacy (VE) against this outcome assumed to be equal to that against 

medically attended acute respiratory illness (ARI) caused by RSV (Pfizer RENOIR trial, including unpublished data from partial season 2 follow up).

b

Incidence rates of RSV hospitalization taken from RSV-NET 2016–2020 (unpublished). VE against RSV-associated hospitalization assumed to be equal to that against medically attended 

lower respiratory tract illness (LRTI) with ≥3 symptoms, caused by RSV (Pfizer RENOIR trial, unpublished).

c Probability of in-hospital death among adults hospitalized for RSV taken from RSV-NET 2016–2020 (unpublished). VE against RSV-associated death assumed to be equal to that against 

medically attended lower respiratory tract illness (LRTI) with ≥3 symptoms, caused by RSV (Pfizer RENOIR trial, unpublished).
27

Pfizer, post-marketing safety requirements and commitments

StudyAim Design Final protocol submission to FDA Study completion date

C3671031a Evaluate risk of GBS Retrospective cohort, 

claims-based November 30, 2023 May 31, 2029

C3671037 Evaluate risk of atrial 

fibrillationb

Active surveillance study November 30, 2023 February 28, 2027

C3671013 (main 

phase 3 trial)

Evaluate safety and 

immunogenicity of 

revaccination

Clinical trial Submitted March 31, 2025

May 31, 2023 Approval Letter - ABRYSVO (fda.gov)

a Post-marketing requirement under Section 505(o) of the Federal Food, Drug, and Cosmetic Act 

b A numerical imbalance in events of atrial fibrillation was noted in the main phase 3 trial, with 10 events in the RSVpreF group and 4 events in the 

placebo group, within 1 month following vaccination.

Vaccines and Related Biological Products Advisory Committee February 28 - March 1, 2023 Meeting Briefing Document- FDA: Applicant Pfizer
28

Benefits and Harms Pfizer bivalent RSVpreF vaccine

▪ How substantial are the desirable anticipated effects among adults 

aged ≥65 years (relative to no RSV vaccine)?

– How substantial is the anticipated protective effect against:

• RSV lower respiratory tract disease (LRTD)

• Medically attended RSV LRTD

• Hospitalization for RSV respiratory illness

• Severe RSV respiratory illness requiring supplemental O2/respiratory 

support

• Death due to RSV respiratory illness

Minimal Small Moderate Large Varies Don’t know
29

Benefits and Harms Pfizer bivalent RSVpreF vaccine

▪ How substantial are the undesirable anticipated effects among 

adults aged ≥65 years (relative to no RSV vaccine)?

– How substantial is the anticipated effect on:

• Serious Adverse Events (SAEs)

• Inflammatory neuropathy (e.g., Guillain-Barré Syndrome)

• Reactogenicity (grade ≥3)

Minimal Small Moderate Large Varies Don’t know
30

Benefits and Harms Pfizer bivalent RSVpreF vaccine

▪ Do the desirable effects outweigh the undesirable effects among 

adults aged ≥65 years?

– What is the balance between the desirable effects relative to 

the undesirable effects?

Favors intervention (Pfizer RSVpreF vaccine)

Favors comparison (no vaccine)

Favors both

Favors neither

Unclear

Minority opinion
31

Benefits and Harms Pfizer bivalent RSVpreF vaccine

▪ How substantial are the desirable anticipated effects among adults 

aged 60–64 years (relative to no RSV vaccine)?

– How substantial is the anticipated protective effect against:

• RSV lower respiratory tract disease (LRTD)

• Medically attended RSV LRTD

• Hospitalization for RSV respiratory illness

• Severe RSV respiratory illness requiring supplemental O2/respiratory 

support

• Death due to RSV respiratory illness

Minimal Small Moderate Large Varies Don’t know
32

Benefits and Harms Pfizer bivalent RSVpreF vaccine

▪ How substantial are the undesirable anticipated effects among 

adults aged 60–64 years (relative to no RSV vaccine)?

– How substantial is the anticipated effect on:

• Serious Adverse Events (SAEs)

• Inflammatory neuropathy (e.g., Guillain-Barré Syndrome)

• Reactogenicity (grade ≥3)

Minimal Small Moderate Large Varies Don’t know
33

Benefits and Harms Pfizer bivalent RSVpreF vaccine

▪ Do the desirable effects outweigh the undesirable effects among 

adults aged 60–64 years?

– What is the balance between the desirable effects relative to 

the undesirable effects?

Favors intervention (Pfizer RSVpreF vaccine)

Favors comparison (no vaccine)

Favors both

Favors neither

Unclear

Minority opinion
34

GRADE: GSK adjuvanted RSVPreF3
35

GSK, Benefits: vaccine efficacy estimates

OutcomeImportance Data sources Vaccine efficacy of a single dose (%)a

(95% confidence interval)

Concerns in certainty 

assessment

Benefits

RSV Lower Respiratory 

Tract Disease (LTRD) Critical

One phase 3 RCTb, 

- 15.3 months mean 

follow up time, 

including season 2c

- 31,932 – 32,023 

person-years under 

surveillance, varied 

by outcome

74.6 (62.1, 83.5)

Vaccine: n=30, Placebo: n=139

Indirectness (serious)d

Medically attended RSV 

LRTD Critical 77.5 (57.9, 89.0)

Vaccine: n=12, Placebo: n=63

Indirectness (serious)d

Hospitalization for RSV 

respiratory illness Important 76.4 (-111, 99.5)

Vaccine: n=1, Placebo: n=5

Indirectness (serious)d

Imprecision (very serious)e

Severe RSV respiratory 

illness requiring 

O2/respiratory support

Important 76.4 (-111, 99.5)

Vaccine: n=1, Placebo: n=5

Indirectness (serious)d

Imprecision (very serious)e

Death due to RSV 

respiratory illness Important Vaccine: n=0/14,677 person-yearsPlacebo: n=0/17,346 person-years

Unable to evaluatef

a Efficacy estimates were independently calculated using counts of events and total person-time available from the GSK pivotal phase 3 trial. Data provided by manufacturer. 

Efficacy was calculated as 1 – incidence rate ratio. Events of each outcome were included if they occurred on or after day 15 after injection. Due to exclusion of follow up time after 

RSVPreF3 dose 2 among participants randomized to annual re-vaccination, person-time in the placebo arm exceeded that in the intervention arm. CDC method of efficacy 

estimation differed from manufacturer method (Poisson model adjusted by season, participant age, & region). Adjustment by season resulted in substantially different estimates.

b RCT = randomized controlled trial. Papi A, et al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. 2023. NEJM. https://doi.org/10.1056/nejmoa2209604

c Mean efficacy follow up time inclusive of person-time after dose 2 of RSVPreF3 was 16.6 months. Median time of efficacy follow up was 17.8 months.

d Underrepresentation of adults aged ≥75 years, adults with congestive heart failure, and frail adults. Exclusion of adults with immune compromise.

e 95% confidence interval for measure of absolute risk included potential for both benefit and harm. Fragility of estimates.

f No RSV-associated deaths were recorded.
36

GSK, Benefits: vaccine efficacy estimates

OutcomeImportance Data sources Vaccine efficacy of a single dose (%)a

(95% confidence interval)

Concerns in certainty 

assessment

Benefits

RSV Lower Respiratory 

Tract Disease (LTRD) Critical

One phase 3 RCTb, 

- 15.3 months mean 

follow up time, 

including season 2c

- 31,932 – 32,023 

person-years under 

surveillance, varied 

by outcome

74.6 (62.1, 83.5)

Vaccine: n=30, Placebo: n=139

Indirectness (serious)d

Medically attended RSV 

LRTD Critical 77.5 (57.9, 89.0)

Vaccine: n=12, Placebo: n=63

Indirectness (serious)d

Hospitalization for RSV 

respiratory illness Important 76.4 (-111, 99.5)

Vaccine: n=1, Placebo: n=5

Indirectness (serious)d

Imprecision (very serious)e

Severe RSV respiratory 

illness requiring 

O2/respiratory support

Important 76.4 (-111, 99.5)

Vaccine: n=1, Placebo: n=5

Indirectness (serious)d

Imprecision (very serious)e

Death due to RSV 

respiratory illness Important Vaccine: n=0/14,677 person-yearsPlacebo: n=0/17,346 person-years

Unable to evaluatef

a Efficacy estimates were independently calculated using counts of events and total person-time available from the GSK pivotal phase 3 trial. Data provided by manufacturer. 

Efficacy was calculated as 1 – incidence rate ratio. Events of each outcome were included if they occurred on or after day 15 after injection. Due to exclusion of follow up time after 

RSVPreF3 dose 2 among participants randomized to annual re-vaccination, person-time in the placebo arm exceeded that in the intervention arm. CDC method of efficacy 

estimation differed from manufacturer method (Poisson model adjusted by season, participant age, & region). Adjustment by season resulted in substantially different estimates.

b RCT = randomized controlled trial. Papi A, et al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. 2023. NEJM. https://doi.org/10.1056/nejmoa2209604

c Mean efficacy follow up time inclusive of person-time after dose 2 of RSVPreF3 was 16.6 months. Median time of efficacy follow up was 17.8 months.

d Underrepresentation of adults aged ≥75 years, adults with congestive heart failure, and frail adults. Exclusion of adults with immune compromise.

e 95% confidence interval for measure of absolute risk included potential for both benefit and harm. Fragility of estimates.

f No RSV-associated deaths were recorded.
37

GSK: RSV lower respiratory tract disease (LRTD)

Age group 

in years

Case split 

(vaccine/placebo)a

Manufacturer-calculated vaccine efficacyb, % (CI)

No adjustment by season Adjusted by season

≥60 (all) 30/139 74.5 (60.0, 84.5) 67.2 (48.2, 80.0)

≥65 25/100 70.3 (53.5, 81.6) 61.2 (39.0, 76.1)

≥70 13/65 76.4 (56.7, 88.1) 69.3 (43.4, 84.6)

≥75 8/24 Not sharedc 49.3 (-18.2, 80.6)c

≥80 4/10 52.6 (-64.2, 89.2)c 38.4 (-118, 86.1)c

a GSK pivotal phase 3 trial (Papi A, et al. NEJM 2023 https://doi.org/10.1056/nejmoa2209604). Events of each outcome were included if they 

occurred on or after day 15 after injection. Median time, across participants, of efficacy follow up was 17.8 months, including unpublished data 

provided by manufacturer from season 2. Total 24,967 participants (31,932 person-years) under surveillance.

b Calculated using Poisson model, adjusted by season and participant age and region. Adjustment by season resulted in efficacy estimates 

substantially different from those estimated by CDC. Due to exclusion of follow up time after dose 2 of RSVPreF3 among participants 

randomized to annual re-vaccination, person-time follow up in the placebo arm exceeded that in the intervention arm.

c Highlighted text indicates that evidence of statistically significant efficacy is lacking.
38

GSK: RSV lower respiratory tract disease (LRTD)

Population

Case split 

(vaccine/ 

placebo)a

Manufacturer-calculated vaccine efficacyb, % (CI)

No adjustment by season Adjusted by season

≥1 pre-existing comorbidity of 

interestc 16/72 74.5 (55.7, 86.1) 66.7 (41.8, 82.0)

≥1 pre-existing cardiorespiratory 

comorbidityd 10/56 80.1 (60.6, 91.0) 73.8 (47.9, 88.2)

Gait speed ≥1.0 m/s (fit) 20/89 73.4 (56.5, 84.5) 66.2 (44.3, 80.4)

Gait speed 0.4–0.99 m/s (pre-frail) 8/47 80.0 (57.3, 91.8) 73.3 (42.4, 89.2)

Gait speed <0.4 m/s or unable to 

complete assessment (frail)

2/1 -116 (-12,800, 88.9)e-148 (-15,800, 88.2)e

a GSK pivotal phase 3 trial (Papi A, et al. NEJM 2023 https://doi.org/10.1056/nejmoa2209604). Events of each outcome were included if they 

occurred on or after day 15 after injection. Median time, across participants, of efficacy follow up was 17.8 months, including unpublished data 

provided by manufacturer from season 2. Total 24,967 participants (31,932 person-years) under surveillance.

b Calculated using Poisson model, adjusted by season and participant age and region. Adjustment by season resulted in efficacy estimates 

substantially different from those estimated by CDC. Due to exclusion of follow up time after dose 2 of RSVPreF3 among participants randomized to 

annual re-vaccination, person-time follow up in the placebo arm exceeded that in the intervention arm.

c COPD, asthma, any chronic respiratory/pulmonary disease, diabetes mellitus, chronic heart failure, advanced liver or renal disease

d COPD, asthma, any chronic respiratory/pulmonary disease, chronic heart failure

e Highlighted text indicates that evidence of statistically significant efficacy is lacking.
39

GSK, Harms: relative risk

OutcomeImportance Data sources Relative risk estimatea

(95% confidence interval)

Concerns in certainty 

assessment

Harms

Serious adverse events (SAEs) Critical One phase 3 RCTb

,

one phase 1/2 RCTc

1.02 (0.91, 1.15)

N=25,174 total participants None serious

Inflammatory neurologic 

events

Important One phase 3 RCTd

one phase 1/2 RCTd

Vaccine: n=0/12,570 participants

Placebo: n=0/12,604 participants Unable to evaluate

Reactogenicity (grade ≥3) Important One phase 3 RCTf

one phase 1/2 RCTg

4.06 (1.97, 8.36)

N=1,955 total participants None serious

a Pooled relative risk estimates were independently calculated using counts of events and participants in the GSK pivotal phase 3 trial (Papi A, et al. NEJM 2023 

https://doi.org/10.1056/nejmoa2209604), as well as from a placebo-controlled phase 1/2 dosing selection study (Leroux-Roels I, et al. J Infect Dis. 2022 

https://doi.org/10.1093/infdis/jiac327). Data provided by manufacturer.

b Up to 6 months after injection

c After dose 1, but before dose 2 (day 61)

d Within 42 days after injection

e No events recorded in studies included in GRADE. One event of Guillain-Barré syndrome (GBS) reported within 42 days after vaccination in a recipient of the 

investigational vaccine in an open label trial without a placebo arm. This study was not included in GRADE assessment due to lack of an unvaccinated 

comparator. Two events of acute disseminated encephalomyelitis (ADEM) reported in a co-administration study of the investigational vaccine with standard 

dose seasonal influenza vaccine. Both cases were reported in the co-administration arm within 42 days after the intervention; none in the sequential 

administration control arm. This study was not included in GRADE assessment due to lack of an unvaccinated comparator.

f Within 7 days after vaccination

g Within 4 days after vaccination

RCT: Randomized control trial
40

GSK, Harms: relative risk

OutcomeImportance Data sources Relative risk estimatea

(95% confidence interval)

Concerns in certainty 

assessment

Harms

Serious adverse events (SAEs) Critical One phase 3 RCTb

,

one phase 1/2 RCTc

1.02 (0.91, 1.15)

N=25,174 total participants None serious

Inflammatory neurologic 

events

Important One phase 3 RCTd

one phase 1/2 RCTd

Vaccine: n=0/12,570 participants

Placebo: n=0/12,604 participants Unable to evaluate

Reactogenicity (grade ≥3) Important One phase 3 RCTf

one phase 1/2 RCTg

4.06 (1.97, 8.36)

N=1,955 total participants None serious

a Pooled relative risk estimates were independently calculated using counts of events and participants in the GSK pivotal phase 3 trial (Papi A, et al. NEJM 2023 

https://doi.org/10.1056/nejmoa2209604), as well as from a placebo-controlled phase 1/2 dosing selection study (Leroux-Roels I, et al. J Infect Dis. 2022 

https://doi.org/10.1093/infdis/jiac327). Data provided by manufacturer.

b Up to 6 months after injection

c After dose 1, but before dose 2 (day 61)

d Within 42 days after injection

e No events recorded in studies included in GRADE. One event of Guillain-Barré syndrome (GBS) reported within 42 days after vaccination in a recipient of the 

investigational vaccine in an open label trial without a placebo arm. This study was not included in GRADE assessment due to lack of an unvaccinated 

comparator. Two events of acute disseminated encephalomyelitis (ADEM) reported in a co-administration study of the investigational vaccine with standard 

dose seasonal influenza vaccine. Both cases were reported in the co-administration arm within 42 days after the intervention; none in the sequential 

administration control arm. This study was not included in GRADE assessment due to lack of an unvaccinated comparator.

f Within 7 days after vaccination

g Within 4 days after vaccination

RCT: Randomized control trial

Total of 3 inflammatory neurologic events reported 

within 42 days of vaccination with RSVpreF3 among 

17,922 older adults across all clinical trials
41

GSK: Total inflammatory neurologic events reported within 42 

days of vaccination across all clinical trials

Participant 

age

Country Reported as Onset Trial Work group case 

review

78 years Japan GBSa, Brighton 

Collaborationb

level 3

9 days 

postvaccination

• Open-label phase 3 trial without a 

placebo control, evaluating the 

immunogenicity of different 

revaccination intervals

Likely GBSa

71 years South 

Africa

ADEMc, fatal*

*Site investigator 

updated diagnoses: 

hypoglycemia & 

dementia

7 days 

postvaccination

• Randomized, blinded co-administration 

study with standard dose seasonal 

influenza vaccine

• Case occurred in the simultaneous 

administration arm of the study

ADEMc cannot be 

ruled out, however, 

other diagnoses 

appear more likely

71 years South 

Africa

ADEMc 22 days 

postvaccination

• Randomized, blinded co-administration 

study with standard dose seasonal 

influenza vaccine

• Case occurred in the simultaneous 

administration arm of the study

ADEMc cannot be 

ruled out, however, 

other diagnoses 

appear more likely

a GBS = Guillain Barre syndrome

b https://brightoncollaboration.us/guillain-barre-and-miller-fisher-syndromes-case-definition-companion-guide/

c ADEM = acute disseminated encephalomyelitis
42

Summary of GRADE for GSK RSVPreF3 vaccine in older adults

OutcomeImportance Design

(# of studies)

FindingsEvidence

type

Benefits

RSV Lower Respiratory Tract 

Disease (LTRD) Critical RCT (1) GSK RSVPreF3 likely reduces RSV LRTD. Moderate

Medically attended RSV 

LRTD Critical RCT (1) GSK RSVPreF3 likely reduces medically attended RSV LRTD. Moderate

Hospitalization for RSV 

respiratory illness Important RCT (1) GSK RSVPreF3 may reduce hospitalization for RSV respiratory illness, but the effect is very uncertain. Very low

Severe RSV respiratory 

illness requiring 

O2/respiratory support

Important RCT (1)

GSK RSVPreF3 may reduce severe RSV respiratory illness requiring 

oxygen supplementation or other respiratory support, but the 

effect is very uncertain.

Very low

Death due to RSV respiratory 

illness Important RCT (1) No events observed Unable to evaluate

Harms

Serious adverse eventsCritical RCT (2) GSK RSVPreF3 results in little to no differences in SAEs. High

Inflammatory neurologic 

events

Important RCT (2) No events observed in placebo-controlled trials. Three cases 

observed in clinical trials without placebo controls.

Unable to 

evaluate

Reactogenicity (grade ≥3) Important RCT (2) GSK RSVPreF3 increases severe reactogenicity events. High
43

Summary of GRADE for GSK RSV vaccine in older adults

Overall evidence rating: Moderate certainty
44

Modeling potential RSV-attributable illnesses prevented:

GSK RSVPreF3

▪ Included in economic analysis performed by U. Michigan, using published incidence 

estimates and RSV-NET estimated annual hospitalizations per 100,000 adults

▪ Timeframe: 2 RSV seasons (assumed duration of vaccine protection)

Number prevented per 1 

million vaccinations among:

Adults aged ≥65 years

Number prevented per 1 

million vaccinations among:

Adults aged 60–64 years

Outpatient visitsa 23,000 18,000

Hospitalizationsb 2,300 890

Deathsc 120 35

a

Incidence rates of RSV illness requiring outpatient visit taken from McLaughlin et al, OFID (2022). Vaccine efficacy (VE) against this outcome assumed to be equal to that against 

medically attended acute respiratory illness (ARI) caused by RSV (GSK AReSVi-006 trial, including unpublished data from season 2 follow up).

b

Incidence rates of RSV hospitalization taken from RSV-NET 2016–2020 (unpublished). VE against RSV-associated hospitalization assumed to be equal to that against medically attended 

lower respiratory tract disease (LRTD) caused by RSV (GSK AReSVi-006 trial, unpublished).

c Probability of in-hospital death among adults hospitalized for RSV taken from RSV-NET 2016–2020 (unpublished). VE against RSV-associated death assumed to be equal to that against 

medically attended lower respiratory tract disease (LRTD) caused by RSV (GSK AReSVi-006 trial, unpublished).
45

GSK, post-marketing safety requirements and commitments

Aim Design Final protocol submission to FDA Study completion date

Evaluate risk of GBS, 

ADEMa

Self-controlled risk interval 

design June 30, 2024 June 30, 2030

Evaluate risk of atrial 

fibrillationb

Self-controlled risk interval 

design June 30, 2024 June 30, 2030

May 23, 2023 Approval Letter - AREXVY (fda.gov)

a Post-marketing requirement under Section 505(o) of the Federal Food, Drug, and Cosmetic Act

b A numerical imbalance in events of atrial fibrillation was noted in the main phase 3 trial, with 7 events in the RSVPreF3 group and 1 event in the 

placebo group, within 1 month following vaccination (dose 1).

Vaccines and Related Biological Products Advisory Committee February 28 - March 1, 2023 Meeting Briefing Document- FDA: Applicant- GSK
46

Benefits and Harms GSK adjuvanted RSVPreF3 vaccine

▪ How substantial are the desirable anticipated effects among adults 

aged ≥65 years (relative to no RSV vaccine)?

– How substantial is the anticipated protective effect against:

• RSV lower respiratory tract disease (LRTD)

• Medically attended RSV LRTD

• Hospitalization for RSV respiratory illness

• Severe RSV respiratory illness requiring supplemental O2/respiratory 

support

• Death due to RSV respiratory illness

Minimal Small Moderate Large Varies Don’t know
47

Benefits and Harms GSK adjuvanted RSVPreF3 vaccine

▪ How substantial are the undesirable anticipated effects among 

adults aged ≥65 years (relative to no RSV vaccine)?

– How substantial is the anticipated effect on:

• Serious Adverse Events (SAEs)

• Inflammatory neuropathy (e.g., Guillain-Barré Syndrome)

• Reactogenicity (grade ≥3)

Minimal Small Moderate Large Varies Don’t know
48

Benefits and Harms GSK adjuvanted RSVPreF3 vaccine

▪ Do the desirable effects outweigh the undesirable effects among 

adults aged ≥65 years?

– What is the balance between the desirable effects relative to 

the undesirable effects?

Favors intervention (GSK RSVPreF3 vaccine)

Favors comparison (no vaccine)

Favors both

Favors neither

Unclear

Minority opinion
49

Benefits and Harms GSK adjuvanted RSVPreF3 vaccine

▪ How substantial are the desirable anticipated effects among adults 

aged 60–64 years (relative to no RSV vaccine)?

– How substantial is the anticipated protective effect against:

• RSV lower respiratory tract disease (LRTD)

• Medically attended RSV LRTD

• Hospitalization for RSV respiratory illness

• Severe RSV respiratory illness requiring supplemental O2/respiratory 

support

• Death due to RSV respiratory illness

Minimal Small Moderate Large Varies Don’t know
50

Benefits and Harms GSK adjuvanted RSVPreF3 vaccine

▪ How substantial are the undesirable anticipated effects among 

adults aged 60–64 years (relative to no RSV vaccine)?

– How substantial is the anticipated effect on:

• Serious Adverse Events (SAEs)

• Inflammatory neuropathy (e.g., Guillain-Barré Syndrome)

• Reactogenicity (grade ≥3)

Minimal Small Moderate Large Varies Don’t know
51

Benefits and Harms GSK adjuvanted RSVPreF3 vaccine

▪ Do the desirable effects outweigh the undesirable effects among 

adults aged 60–64 years?

– What is the balance between the desirable effects relative to 

the undesirable effects?

Favors intervention (GSK RSVPreF3 vaccine)

Favors comparison (no vaccine)

Favors both

Favors neither

Unclear

Minority opinion
Resource Use

Is an RSV vaccine program for older adults a reasonable and efficient 

allocation of resources?
53

Work group considerations

▪ RSV vaccination for older adults could be a cost-effective intervention

▪ There is substantial uncertainty in the net societal costs of an RSV 

vaccination program for older adults, driven by:

– Uncertainty in vaccine acquisition cost

• Current assumptions: $200 Pfizer RSVpreF, $270 GSK RSVPreF3

– Uncertainty in incidence of RSV illness (e.g., hospitalization)

– Uncertainty in duration of protection from RSV vaccination

• Current assumption: 2 RSV seasons

▪ Vaccination of older age groups would be more cost effective than 

vaccination of younger age groups
54

Resource Use

▪ Is use of Pfizer bivalent RSVpreF vaccine among adults aged 

≥65 years a reasonable and efficient allocation of resources, 

compared with no RSV vaccine?

▪ Is use of GSK adjuvanted RSVPreF3 vaccine among adults aged 

≥65 years a reasonable and efficient allocation of resources, 

compared with no RSV vaccine?

No Probably No Probably Yes Yes Varies Don’t know
55

Resource Use

▪ Is use of Pfizer bivalent RSVpreF vaccine among adults aged 

60–64 years a reasonable and efficient allocation of resources, 

compared with no RSV vaccine?

▪ Is use of GSK adjuvanted RSVPreF3 vaccine among adults aged 

60–64 years a reasonable and efficient allocation of resources, 

compared with no RSV vaccine?

No Probably No Probably Yes Yes Varies Don’t know
Equity

What would be the impact on health equity of recommending RSV 

vaccines in older adults?
57

The Work Group discussed multiple equity concerns. 

▪ Not all persons experience the same risk of RSV disease. 

▪ An RSV vaccine might increase equity by protecting those 

disproportionately impacted by RSV. 

▪ However, if access or uptake of the vaccine is not equal, an 

RSV vaccine might decrease equity.

▪ The age groups in which the vaccine might be recommended 

were felt to have important equity implications.
First the Work Group considered the impact on equity 

of a recommendation for RSV vaccination in adults 

aged 65 years and older. 
Anticipated impact on equity of an age-based recommendation 

for RSV vaccination in adults ≥65

RSV vaccination in adults aged ≥65 years might increase equity by decreasing RSV burden 

among persons from racial and ethnic minority groups and in persons with lower income 

levels.
Next the Work Group considered the impact on equity 

of a recommendation for RSV vaccination in adults 

aged 60–64 years.
61

Age of adults hospitalized with RSV, by race and 

ethnicity, RSV-NET

N Median age, years 

(interquartile range)

All 9,163 70 (58–81)

Race and ethnicity

White, non-Hispanic 5,596 73 (62–83)

Black, non-Hispanic 1,731 60 (50–70)

Hispanic 713 65 (50–77)

Asian or Pacific Islander, non-Hispanic 518 77 (64–85)

American Indian or Alaska Native, 

non-Hispanic

56 57 (47–71)

CDC RSV-NET data 2015–2020 (unpublished). https://www.cdc.gov/rsv/research/rsv-net/index.html
62

Age of adults hospitalized with RSV, by race and 

ethnicity, RSV-NET

N Median age, years 

(interquartile range)

All 9,163 70 (58–81)

Race and ethnicity

White, non-Hispanic 5,596 73 (62–83)

Black, non-Hispanic 1,731 60 (50–70)

Hispanic 713 65 (50–77)

Asian or Pacific Islander, non-Hispanic 518 77 (64–85)

American Indian or Alaska Native, 

non-Hispanic

56 57 (47–71)

CDC RSV-NET data 2015–2020 (unpublished). https://www.cdc.gov/rsv/research/rsv-net/index.html
Number of chronic conditions by age among Asian, Black, Latino/Hispanic, and 

White adults in the National Health Interview Survey (NHIS), 1999 to 2018

Source: Caraballo C, Herrin J, Mahajan S, et 

al. Temporal Trends in Racial and Ethnic 

Disparities in Multimorbidity Prevalence in 

the United States, 1999-2018. Am J Med. 

2022;135(9):1083-1092.e14. 

doi:10.1016/j.amjmed.2022.04.010
Number of chronic conditions by age among Asian, Black, Latino/Hispanic, and 

White adults in the National Health Interview Survey (NHIS), 1999 to 2018

Source: Caraballo C, Herrin J, Mahajan S, et 

al. Temporal Trends in Racial and Ethnic 

Disparities in Multimorbidity Prevalence in 

the United States, 1999-2018. Am J Med. 

2022;135(9):1083-1092.e14. 

doi:10.1016/j.amjmed.2022.04.010
Number of chronic conditions by age among Asian, Black, Latino/Hispanic, and 

White adults in the National Health Interview Survey (NHIS), 1999 to 2018

Source: Caraballo C, Herrin J, Mahajan S, et 

al. Temporal Trends in Racial and Ethnic 

Disparities in Multimorbidity Prevalence in 

the United States, 1999-2018. Am J Med. 

2022;135(9):1083-1092.e14. 

doi:10.1016/j.amjmed.2022.04.010
▪ Prevalence of multimorbidity 

(≥2 concurrent conditions) 

diverged between Black 

individuals and White 

individuals

▪ Reached maximum difference 

of 10% among those aged 60-

64 years

Difference in prevalence of multiple chronic conditions by age and 

race/ethnicity, National Health Interview Survey, 1999 to 2018

Source: Caraballo C, Herrin J, Mahajan S, et al. Temporal Trends in Racial and Ethnic Disparities in Multimorbidity Prevalence in the United States, 1999-2018. Am J Med. 

2022;135(9):1083-1092.e14. doi:10.1016/j.amjmed.2022.04.010
RSV vaccination in adults aged ≥65 years might increase equity by decreasing RSV burden 

among persons from racial and ethnic minority groups and persons with lower income 

levels.

An RSV vaccination recommendation that excludes adults aged 60-64 years might 

decrease equity by excluding persons from racial and ethnic minority groups that would 

benefit from the vaccine at earlier ages due to risk conditions. 

Anticipated impact on equity of an age-based recommendation 

for RSV vaccination in adults ≥65
68

Shared clinical decision-making 

▪ One policy option that the Work Group discussed to address the varied 

risk of severe RSV disease (e.g., hospitalization) among 60–64 year-olds 

is shared clinical decision-making (SCDM) for adults aged 60–64 years. 

▪ Ideally, this would allow adults aged 60–64 years at high risk of RSV 

hospitalization to be vaccinated and decrease age-based racial and 

ethnic health disparities. 

▪ Prior experience with SCDM might inform the expected impact on 

equity.
69

ACIP recommendations for vaccination based on shared clinical decisionmaking (SCDM) that appear (or appeared) on the tables and/or notes of the 

immunization schedules

▪ Historical: Pneumococcal conjugate vaccination (PCV13) for adults aged 65 years 

and older who do not have an immunocompromising condition, cerebrospinal fluid 

leak, or cochlear implant (recommendation revised in 2021 with introduction of 

PCV15 and PCV20)

▪ Historical: Hepatitis B (HepB) vaccination for adults aged 60 years and older with 

diabetes mellitus (recommendation revised in 2022)

▪ Meningococcal B (MenB) vaccination for adolescents and young adults aged 16–23 

years

▪ Human papillomavirus (HPV) vaccination for adults aged 27–45 years
70

History of Hepatitis B and SCDM

▪ In 2011, ACIP recommended Hepatitis B vaccination for all unvaccinated adults with 

diabetes mellitus aged <60 years but for unvaccinated adults with diabetes mellitus 

aged ≥60 years, ACIP recommended Hepatitis B vaccination at the discretion of 

their healthcare provider.

▪ (This recommendation was revised in 2022. Now HepB vaccination is universally 

recommended for adults aged 19–59 years and adults aged ≥60 years with risk 

factors for hepatitis B; adults aged ≥60 years without known risk factors for 

hepatitis B may also receive HepB vaccines). 

Source: Weng MK, Doshani M, Khan MA, et al. Universal Hepatitis B Vaccination in Adults Aged 19–59 Years: Updated Recommendations of the 

Advisory Committee on Immunization Practices — United States, 2022. MMWR Morb Mortal Wkly Rep 2022;71:477–483. 

DOI: http://dx.doi.org/10.15585/mmwr.mm7113a1external icon.
71

Hep B vaccine coverage remained suboptimal when recommended to be 

given at provider discretion 

▪ Lu et al. analyzed 2014–2018 NHIS 

data to determine hepatitis B 

vaccination coverage (≥3 doses) 

among adults ≥60 years by 

diabetes mellitus status

▪ Hepatitis B vaccination coverage 

remained low among older adults

with diabetes mellitus even 7 years 

after the recommendation was 

made

Source: Lu PJ, Hung MC, Srivastav A, Williams WW, Harris AM. Hepatitis B Vaccination Among Adults With Diabetes Mellitus, U.S., 2018. Am J Prev Med. 2021 Nov;61(5):652-664. doi: 

10.1016/j.amepre.2021.04.029. Epub 2021 Jul 20. PMID: 34294463; PMCID: PMC9077536.

Race and 

ethnicity 

Vaccination

coverage with ≥3 Hep B 

doses

among adults ≥60 with

diabetes mellitus

Vaccination coverage

with ≥3 Hep B doses 

among

adults ≥60 without 

diabetes mellitus

All 15.3 (13.3 – 17.4) 15.9 (14.8-17.0)

White, nonHispanic15.5 (13.1-18.1) 15.9 (14.7-17.2)

Black, nonHispanic17.3 (12.2-23.9) 13.4 (10.5-17.2)

Hispanic 9.2 (4.9-16.7) 16.0 (12.0-21.0)

Asian, nonHispanic 15.7 (8.1-28.2) 18.4 (13.4-24.8)
72

Hep B vaccine coverage remained suboptimal when recommended to be 

given at provider discretion 

▪ Lu et al. analyzed 2014–2018 NHIS 

data to determine hepatitis B 

vaccination coverage (≥3 doses) 

among adults ≥60 years by 

diabetes mellitus status

▪ Hepatitis B vaccination coverage 

remained low among older adults

with diabetes mellitus even 7 years 

after the recommendation was 

made

▪ However, coverage may have been 

higher among Black, non-Hispanic 

older adults with diabetes mellitus

Source: Lu PJ, Hung MC, Srivastav A, Williams WW, Harris AM. Hepatitis B Vaccination Among Adults With Diabetes Mellitus, U.S., 2018. Am J Prev Med. 2021 Nov;61(5):652-664. doi: 

10.1016/j.amepre.2021.04.029. Epub 2021 Jul 20. PMID: 34294463; PMCID: PMC9077536.

Race and 

ethnicity 

Vaccination

coverage with ≥3 Hep B 

doses

among adults ≥60 with

diabetes mellitus

Vaccination coverage

with ≥3 Hep B doses 

among

adults ≥60 without 

diabetes mellitus

All 15.3 (13.3 – 17.4) 15.9 (14.8-17.0)

White, nonHispanic15.5 (13.1-18.1) 15.9 (14.7-17.2)

Black, nonHispanic17.3 (12.2-23.9) 13.4 (10.5-17.2)

Hispanic 9.2 (4.9-16.7) 16.0 (12.0-21.0)

Asian, nonHispanic 15.7 (8.1-28.2) 18.4 (13.4-24.8)
73

In studies assessing knowledge, attitude, and practices around SCDM for 

other vaccines, providers have reported mixed views and understanding 

of recommendations

1. Kempe A, Lindley MC, O'Leary ST, et al. Shared Clinical Decision-Making Recommendations for Adult Immunization: What Do Physicians Think?. J Gen Intern Med. 2021;36(8):2283-2291. 

doi:10.1007/s11606-020-06456-z

2. Hurley LP, O'Leary ST, Kobayashi M, et al. Physician survey regarding updated PCV13 vaccine recommendations for adults ≥65 years. J Am Geriatr Soc. 2021;69(9):2612-2618. doi:10.1111/jgs.17274

• Some think that SCDM requires more time 

than routine recommendations, that SCDM 

creates confusion, and many do not know 

vaccines recommended for SCDM would be 

covered by most health insurance1,2

• Providers unsure of what points to emphasize 

in discussions with patients2

• Some in favor of SCDM recommendations 

because they give more flexibility in decisions 

about use of a vaccine1
74

Brief summary of SCDM equity considerations

▪ Ideally SCDM would increase access for adults aged 60–64 years with 

medical risk factors for severe RSV disease (disproportionately in racial 

and ethnic groups impacted by RSV at earlier ages)

▪ Limited evidence regarding the impact of conditional 

recommendations, like SCDM, in older adults suggests they may not 

substantially increase uptake in the target population

▪ However, without a recommendation for adults aged 60–64 years, 

adults with medical risk factors for severe RSV disease would likely face 

additional barriers to RSV vaccination, increasing health disparities
Anticipated impact on equity

RSV vaccination in adults aged ≥65 years might increase equity by decreasing RSV burden 

among persons from racial and ethnic minority groups and persons with lower income 

levels.

RSV vaccination that excludes adults aged 60-64 years might decrease equity by 

excluding persons from racial and ethnic minority groups that would benefit from the 

vaccine at earlier ages due to risk conditions. 

RSV vaccination that includes both adults aged 65 and older and adults aged 60-64 years 

under shared clinical decision-making (SCDM) would increase access for adults 60–64 

with medical risk factors for severe RSV disease (disproportionately in racial and ethnic 

groups impacted by RSV at earlier ages). However, SCDM may not substantially increase 

uptake in the target population.
76

Equity

▪ What would be the impact on health equity of recommending RSV 

vaccines in adults aged ≥65 years?

Reduced

Probably reduced

Probably no impact

Probably increased

Increased

Varies

Don’t know
77

Equity

▪ What would be the impact on health equity of recommending RSV 

vaccines in adults aged 60–64 years?

Reduced

Probably reduced

Probably no impact

Probably increased

Increased

Varies

Don’t know

Minority opinion
Summary
79

Domain Question Work Group Judgements

Adults aged ≥65 years Pfizer GSK

Public Health 

Problem Is RSV of public health importance? Yes

Benefits and 

Harms

How substantial are the desirable anticipated effects? Moderate Moderate

How substantial are the undesirable anticipated effects? Small Small

Do the desirable effects outweigh the undesirable effects? Favors intervention Favors intervention

What is the overall certainty of the evidence profile? Moderate Moderate

Values

Does 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? Important variability/Probably 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 Use Is the intervention a reasonable and efficient allocation of 

resources? Probably yes Probably yes

Equity What would be the impact on health equity? Probably increased/Probably no impact
80

Domain Question Work Group Judgements

Adults aged 60–64 years Pfizer GSK

Public Health 

Problem Is RSV of public health importance? Yes

Benefits and 

Harms

How substantial are the desirable anticipated effects? Small – Moderate Small – Moderate

How substantial are the undesirable anticipated effects? Small Small

Do the desirable effects outweigh the undesirable effects? Unclear Unclear

What is the overall certainty of the evidence profile? Moderate Moderate

Values

Does 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? Important variability/Probably 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 Use Is the intervention a reasonable and efficient allocation of 

resources? Probably no Probably no

Equity What would be the impact on health equity? Unclear
81

Work Group interpretation (part 1)

▪ Pfizer’s bivalent RSVpreF and GSK’s adjuvanted RSVPreF3 vaccines both 

have demonstrated significant efficacy against lower respiratory tract 

illness caused by RSV among older adults over at least two seasons

– Trials were underpowered to show efficacy in the oldest adults and in adults 

who are frail

– Trials were underpowered to show efficacy against RSV hospitalization

• Efficacy against symptomatic illness may indicate efficacy against more 

severe disease

▪ RSV vaccination has the potential to prevent considerable morbidity from 

RSV disease among older adults, particularly in those with chronic medical 

conditions and those who are frail (e.g., long-term care facility residents)
82

Work Group interpretation (part 2)

▪ Cases of inflammatory neurologic events have been reported within 42 

days after vaccination with each RSV vaccine

▪ Clinical trials were not sufficiently powered to determine whether the 

small number of cases occurred due to random chance

▪ Whether there is an increased risk of GBS or other inflammatory 

neurologic events from RSV vaccination is not known at this time

▪ Post-licensure surveillance for both safety and vaccine effectiveness will be 

critical
83

Choice of age threshold at which to recommend RSV vaccines

Pros Cons

Age ≥65 years 

only

• Greater risk of RSV disease and therefore 

more favorable population-wide balance 

of risks and benefits of vaccination (in 

light of cases of inflammatory neurologic 

events observed)

• Aligns with recommendations for highdose and adjuvanted influenza vaccines, 

and universal pneumococcal vaccination

• Lost opportunity to prevent additional disease 

in the 60–64 age group, who are 

disproportionately from racial and ethnic 

groups impacted by RSV at earlier ages

Also in ages 

60–64 years

• Potential to prevent a greater total 

burden of disease (e.g., number of 

hospitalizations)

• Increases access to adults 60–64 with 

medical risk factors for severe RSV 

disease (disproportionately in racial and 

ethnic groups impacted by RSV at earlier 

ages)

• Risk/benefit balance depends on the patient 

population that seeks and receives vaccination 

among those 60–64

• Uninsured adults would face financial barriers 

obtaining vaccination (disproportionately aged 

60–64 in racial, ethnic and socioeconomic 

groups at greater risk of severe RSV)

• May experience more difficulty achieving 

clinician adoption of the recommendation 

among patients 60–64

• Less efficient allocation of societal resources
84

Evidence to Recommendations Framework

Summary: Work Group Interpretations

▪ Work Group interpretations were similar for:

– Pfizer bivalent RSVpreF

– GSK adjuvanted RSVPreF3
85

Evidence to Recommendations Framework

Summary: Work Group Interpretations (Pfizer RSVpreF, GSK RSVPreF3)

Balance of 

consequences

Undesirable 

consequences 

clearly outweigh 

desirable 

consequences in 

most settings

Undesirable 

consequences 

probably 

outweigh 

desirable 

consequences in 

most settings

The balance 

between 

desirable and 

undesirable 

consequences is 

closely balanced 

or uncertain

Desirable 

consequences 

probably 

outweigh 

undesirable 

consequences in 

most settings

Desirable 

consequences 

clearly outweigh 

undesirable 

consequences in 

most settings

There is 

insufficient 

evidence to 

determine the 

balance of 

consequences

Among adults aged ≥65 years:

Balance of 

consequences

Undesirable 

consequences 

clearly outweigh 

desirable 

consequences in 

most settings

Undesirable 

consequences 

probably 

outweigh 

desirable 

consequences in 

most settings

The balance 

between 

desirable and 

undesirable 

consequences is 

closely balanced 

or uncertain

Desirable 

consequences 

probably 

outweigh 

undesirable 

consequences in 

most settings

Desirable 

consequences 

clearly outweigh 

undesirable 

consequences in 

most settings

There is 

insufficient 

evidence to 

determine the 

balance of 

consequences

Among adults aged 60–64 years:

Minority opinion
86

Evidence to Recommendations Framework

Summary: Work Group Interpretations (Pfizer RSVpreF, GSK RSVPreF3)

Type of recommendation, adults aged ≥65 years

We do not recommend the intervention

We recommend the intervention for individuals based on shared clinical decision-making

We recommend the intervention

Minority opinion
87

Evidence to Recommendations Framework

Summary: Work Group Interpretations (Pfizer RSVpreF, GSK RSVPreF3)

Type of recommendation, adults aged ≥65 years

We do not recommend the intervention

We recommend the intervention for individuals based on shared clinical decision-making

We recommend the intervention

Type of recommendation, adults aged 60–64 years

We do not recommend the intervention

We recommend the intervention for individuals based on shared clinical decision-making

We recommend the intervention

Minority opinion
88

Proposed ACIP Voting Language

• Adults 65 years of age and older are recommended to receive 

a single dose of RSV vaccine.

• Individual adults aged 60–64 years may receive a single dose 

of RSV vaccine, using shared clinical decision-making based on 

risk assessment.
89

Acknowledgements 

▪ Karen Broder

▪ Doug Campos-Outcalt

▪ Katherine Fleming-Dutra

▪ Monica Godfrey

▪ Fiona Havers

▪ Anne Hause

▪ Jefferson Jones

▪ Andrew Leidner

▪ Meredith McMorrow

▪ Rebecca Morgan

▪ Dani Moulia

▪ Neil Murthy

▪ Sara Oliver

▪ Christine Olson

▪ Ismael Ortega Sanchez

▪ David Shay

▪ Amanda Payne

▪ Huong Pham

▪ Jamison Pike

▪ Mila Prill

▪ Lauren Roper

▪ Hannah Rosenblum

▪ Jim Sejvar

▪ Tom Shimabukuro

▪ Evelyn Twentyman 

▪ Megan Wallace

▪ Michael Whitaker

▪ Patricia Wodi