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 Updates

Pfizer Maternal RSVpreF Vaccine

ACIP General Meeting

September 22, 2023

Katherine E. Fleming-Dutra, MD

Co-lead, Respiratory Syncytial Virus Vaccines – Pediatric/Maternal Work Group

Coronavirus and Other Respiratory Viruses Division

National Center for Immunization and Respiratory Diseases
2

▪ Should Pfizer RSVpreF vaccine be recommended for pregnant people to be given 

during 32 through 36 weeks gestation to prevent RSV lower respiratory tract infection 

in infants?

Policy question

RSVpreF is a bivalent recombinant stabilized prefusion F protein subunit vaccine.

Key points that have been updated since the June ACIP presentation are highlighted on the slides. 
3

▪ On August 21, 2023, FDA approved Pfizer RSVpreF vaccine for use in pregnant people 

as a single dose to be given at 32 through 36 weeks gestation

▪ In the phase 2b and 3 trials, vaccination was given during 24 through 36 weeks 

gestation 

▪ Throughout the presentation, these will be denoted as

• Approved dosing interval (32–36 weeks gestation)

• Trial dosing interval (24–36 weeks gestation)

FDA approval for RSVpreF vaccine

FDA Approves First Vaccine for Pregnant Individuals to Prevent RSV in Infants | FDA

Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document- FDA

Same Pfizer RSV vaccine, formulation and dose approved for use in adults ages 60 years and older
4

Population Pregnant people

Intervention Pfizer RSVpreF vaccine given at 32–36 weeks gestation

Comparison No vaccine

Outcomes ▪ Medically attended RSV-associated lower respiratory tract infection in infants

▪ Hospitalization for RSV-associated lower respiratory tract infection in infants

▪ Intensive care unit (ICU) admission from RSV hospitalization in infants

▪ Mechanical ventilation from RSV hospitalization in infants

▪ RSV-associated death in infants

▪ All-cause hospitalization for lower respiratory tract infection in infants

▪ All-cause medically attended lower respiratory tract infection in infants

▪ Serious adverse events in pregnant people

▪ Reactogenicity (grade 3+) in pregnant people

▪ Serious adverse events in infants

▪ Preterm birth (<37 weeks gestation)

Evidence to Recommendations (EtR) framework

PICO question
5

Evidence 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?
6

EtR Domain: Public Health Problem

Is the problem of public health importance?
7

▪ Most (68%) infants are infected in the first year of life and 

nearly all (97%) by age 2 years2

▪ 2–3% of young infants will be hospitalized for RSV3,4,5

▪ RSV is a common cause of lower respiratory tract infection 

in infants 

▪ Highest RSV hospitalization rates occur in first months of 

life and risk declines with increasing age in early 

childhood3,5

▪ 79% of children hospitalized with RSV aged <2 years had no 

underlying medical conditions3

RSV is the leading cause of hospitalization in U.S. 

infants1

1Suh et al. JID 2022; 2Glezen et al, Arch Dis Child, 1986; 3Hall et al, Pediatrics, 2013; 4Langley & Anderson, PIDJ, 2011; 5CDC NVSN data

Image: Goncalves et al. Critical Care 

Research and Practice 2012
8

▪ Is RSV among infants of public health importance? 

Public Health Problem: Work Group interpretation

No Probably 

No

Probably 

Yes Yes Varies Don’t know
9

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?
10

GRADE outcomes, importance, and data sources: Pfizer 

maternal RSVpreF vaccine

RCT = Randomized controlled trial; ICU= intensive care unit

1 Three options: Critical; Important but not critical; Not important for decision making

2 Among phase 2b trial participants, only those who received the vaccine formulation of the phase 3 trial or placebo were included

Outcome Importance1 Data sources

Benefits

Medically attended RSV-associated lower respiratory tract infection in infants Critical Phase 3 RCT

Hospitalization for RSV-associated lower respiratory tract infection in infants Critical Phase 3 RCT

ICU admission from RSV hospitalization in infants Important Phase 3 RCT

Mechanical ventilation from RSV hospitalization in infants Important Phase 3 RCT

RSV-associated death in infants Important Phase 3 and phase 2b2 RCT

All-cause medically attended lower respiratory tract infection in infants Important Phase 3 RCT

All-cause hospitalization for lower respiratory tract infection in infants Important Phase 3 RCT

Harms

Serious adverse events in pregnant people Critical Phase 3 and phase 2b2 RCT

Reactogenicity (grade 3+) in pregnant people Important Phase 3 and phase 2b2 RCT

Serious adverse events in infants Critical Phase 3 and phase 2b2 RCT

Preterm birth (<37 weeks gestation) Critical Phase 3 and phase 2b2 RCT
11

Data available for GRADE and Benefits and Harms

Trial phase Dosing interval Number of Participants* Decision regarding use in GRADE

Phase 2b trial1 Trial dosing 

interval (24–36 

weeks gestation)

Vaccine (received phase 3 dose 

and formulation): 115

Placebo: 117

Yes. Data for GRADE were limited to participants 

who received placebo or phase 3 vaccine 

formulation and only included for safety 

outcomes. Study was not designed to assess 

efficacy.

Phase 2b trial1 Approved dosing 

interval (32–36 

weeks gestation)

Vaccine (received phase 3 dose 

and formulation): 45

Placebo: 44

No. Safety data are further limited by small 

sample size. Presented as supplemental data.

Phase 3 trial published 

analyses1,2,3

Trial dosing 

interval (24–36 

weeks gestation)

Efficacy set / Safety set

Vaccine: 3495 / 3682

Placebo: 3480 / 3675

Yes. Trial was designed and powered using a 24–

36 weeks dosing interval.

Phase 3 trial, post-hoc 

analysis1

Approved dosing 

interval (32–36 

weeks gestation)

Efficacy set / Safety set

Vaccine: 1572 / 1653

Placebo: 1539 / 1632

No. Trial was not powered for this interval for 

efficacy, and safety data would be limited in 

power to detect harms. Presented as 

supplemental data.

*For phase 2b trial and phase 3 trial safety set, number of maternal participants are listed. For phase 3 trial efficacy set, number of infants participants are listed.

1 Data provided by Pfizer

2 Kampmann et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants - PubMed (nih.gov)

3 Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document- FDA
12

Effect estimates and concerns in certainty of assessment, 

benefits: Pfizer maternal RSVpreF vaccine

RCT= randomized controlled trial; CI= confidence interval; ICU= intensive care unit 

1 Three options: Critical; Important but not critical; Not important for decision making

2 Vaccine efficacy was calculated as 1–(P/[1–P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. The confidence interval was adjusted using the Bonferroni 

procedure and accounting for the primary endpoints results. Efficacy is from full phase 3 trial data, using trial dosing interval (24–36 weeks gestation).

3 Serious concern for imprecision due to the width of the confidence interval containing estimates for which different policy decisions might be considered

4 Vaccine efficacy was calculated as 1–(P/[1–P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. Efficacy is from full phase 3 trial data, using trial dosing interval 

(24–36 weeks gestation).

5 Very serious concern for imprecision due to the width of the confidence interval containing estimates for which different policy decisions might be considered and fragility of the estimate

6 Among phase 2b trial participants, only those who received the vaccine formulation of the phase 3 trial or placebo were included

Outcome Importance1 Data sources Manufacturer 

calculated vaccine efficacy

Concerns in certainty 

assessment

Benefits

Medically attended RSV-associated lower respiratory tract infection in 

infants (0–180 days)

Critical Phase 3 RCT 51.3% (97.58% CI: 29.4, 66.8)2 None

Hospitalization for RSV-associated lower respiratory tract infection in 

infants (0–180 days)

Critical Phase 3 RCT 56.8% (99.17% CI: 10.1, 80.7) 2Imprecision (serious)3

ICU admission from RSV hospitalization in infants (0–180 days) Important Phase 3 RCT 42.9% (95% CI: -124.8, 87.7)4Imprecision (very 

serious)5

Mechanical ventilation from RSV hospitalization in infants (0–180 days) Important Phase 3 RCT 100% (95% CI: -9.1, 100)4Imprecision (very 

serious)5

RSV-associated death in infants Important Phase 3 and 

phase 2b6 RCT

1 RSV-associated death occurred in the placebo arm of the 

phase 3 trial that was recorded at day 120 after birth. No RSVassociated deaths were recorded in the phase 2b trial.

All-cause medically attended lower respiratory tract infection in infants 

(0–180 days)

Important Phase 3 RCT 2.5% (99.17% CI: -17.9, 19.4)2Imprecision (serious)3

All-cause hospitalization for lower respiratory tract infection in infants 

(0–180 days)

Important Phase 3 RCT 28.9% (95% CI: -2.0, 50.8)4Imprecision (serious)3
13

Effect estimates and concerns in certainty of assessment, 

harms: Pfizer maternal RSVpreF vaccine

RCT = Randomized-controlled trial

1 Three options: Critical; Important but not critical; Not important for decision making

2 Pooled relative risk estimates were independently calculated using counts of events and participants in the phase 3 trial interim analysis, and phase 2b trial among those who received the 

phase 3 vaccine formulation or placebo.

3 Serious concern for indirectness as 55% of the Phase 3 RCT and 62% of the Phase 2b RCT did not receive vaccine or placebo in the approved dosing interval (32–36 weeks gestation). In the 

approved dosing interval, there is less opportunity for serious adverse events, including preterm birth/delivery, compared to the trial dosing interval (24–36 weeks gestation).

4 Serious concern for imprecision due to the width of the confidence interval containing estimates for which different policy decisions might be considered

5 Serious concern for indirectness as these data only include systemic reactions. When selecting the a priori harm outcomes, the Work Group defined reactogenicity as both local and systemic 

reactions.

6 Very serious concern for imprecision due to the width of the confidence interval containing estimates for which different policy decisions might be considered and not meeting optimal 

information size requirements

Outcome Importance1 Data sources Relative Risk2 (95% 

confidence interval)

Concerns in certainty 

assessment

Harms

Serious adverse events in pregnant people Critical Phase 3 and 

phase 2b RCT

1.06 (0.95, 1.17) Indirectness (serious)3 and

Imprecision (serious)4

Reactogenicity (grade 3+) in pregnant people Important Phase 3 and 

phase 2b RCT

0.97 (0.72, 1.31) Indirectness (serious)5

Serious adverse events in infants Critical Phase 3 and 

phase 2b RCT

1.01 (0.91, 1.11) Indirectness (serious)3 and 

Imprecision (serious)4

Preterm birth (<37 weeks gestation) Critical Phase 3 and 

phase 2b RCT

1.20 (0.99, 1.46) Indirectness (serious)3 and 

Imprecision (very serious)6
14

Summary of GRADE: Pfizer maternal RSVpreF vaccine

Outcome Importance Design (# of 

studies)

Findings Evidence Type

Benefits

Medically attended RSV-associated lower respiratory 

infection in infants 

Critical RCT (1) Pfizer RSVpreF maternal vaccine is effective in preventing medically 

attended RSV-associated lower respiratory infection in infants 

High

Hospitalization for RSV-associated lower respiratory 

tract infection in infants 

Critical RCT (1) Pfizer RSVpreF maternal vaccine may be effective in preventing 

hospitalization for RSV-associated lower respiratory tract infection in 

infants 

Moderate

ICU admission from RSV hospitalization in infants Important RCT (1) Pfizer RSVpreF maternal vaccine may be effective in preventing ICU 

admission for RSV hospitalization in infants

Low

Mechanical ventilation from RSV hospitalization in 

infants 

Important RCT (1) Pfizer RSVpreF maternal vaccine may be effective in preventing 

mechanical ventilation for RSV hospitalization in infants

Low

RSV-associated death in infants Important RCT (2) 1 event observed in a placebo recipient among both trials Not evaluated

All-cause medically attended lower respiratory tract 

infection in infants 

Important RCT (1) Pfizer RSVpreF maternal vaccine is not effective in preventing allcause medically attended lower respiratory tract infection in infants Moderate

All-cause hospitalization for lower respiratory tract 

infection in infants 

Important RCT (1) Pfizer RSVpreF maternal vaccine may be effective in preventing allcause hospitalization for lower respiratory tract infection in infantsModerate

Harms

Serious adverse events in pregnant people Critical RCT (2) SAEs in pregnant people were balanced between vaccine and placebo 

groups

Low

Reactogenicity (grade 3+) in pregnant people Important RCT (2) Reactogenicity in pregnant people was balanced between vaccine and 

placebo groups

Moderate

Serious adverse events in infants Critical RCT (2) SAEs in infants were balanced between vaccine and placebo groups Low

Preterm birth (<37 weeks gestation) Critical RCT (2) Preterm births were unbalanced between vaccine and placebo groups Very low

RCT = Randomized-controlled trial
15

Summary of GRADE: Pfizer maternal RSVpreF vaccine

The overall evidence type is driven by the lowest quality of evidence for critical outcomes, and here is driven by the evidence rating 

for the critical harm of preterm birth being very low. 

Overall 

evidence type: 

Very Low
16

Effect estimates, benefits: Pfizer maternal RSVpreF vaccine 

comparing trial vs approved dosing interval

CI= confidence interval; ICU=Intensive care unit

1 Vaccine efficacy was calculated as 1–(P/[1–P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. Confidence intervals that are not 95% were adjusted using the Bonferroni 

procedure and accounting for the primary endpoints results. 

2 Vaccine efficacy was calculated as 1-(hP/[1-P]), where P is the number of cases in the RSVpreF group divided by the total number of cases and h is the ratio of number of participants at risk in the placebo group to 

the number of participants at risk in the RSVpreF group.

Outcome

Trial dosing interval

(24–36 weeks gestation)

Approved dosing interval 

(32–36 weeks gestation)

Manufacturer calculated 

vaccine efficacy (CI)1

Manufacturer calculated vaccine 

efficacy (95% CI)2

Benefits

Medically attended RSV-associated lower respiratory tract 

infection in infants (0–180 days) 51.3% (97.58% CI: 29.4, 66.8) 57.3% (95% CI: 29.8, 74.7)

Hospitalization for RSV-associated lower respiratory tract 

infection in infants (0–180 days) 56.8% (99.17% CI: 10.1, 80.7) 48.2% (95% CI: -22.9, 79.6)

ICU admission from RSV hospitalization in infants (0–180 days) 42.9% (95% CI: -124.8, 87.7) 1 event in the vaccine group 

2 events in the placebo group 

Mechanical ventilation from RSV hospitalization in infants (0–

180 days)

100% (95% CI: -9.1, 100) 0 events in the vaccine group 

2 events in the placebo group 

All-cause medically attended lower respiratory tract infection in 

infants (0–180 days)

2.5% (99.17%: -17.9, 19.4) 7.3% (95% CI: -15.7, 25.7)

All-cause hospitalization for lower respiratory tract infection in 

infants (0–180 days)

28.9% (95% CI: -2.0, 50.8) 34.7% (95% CI: -18.8, 64.9)
17

▪ As defined in the Pfizer trial, this outcome 

was not included by the Work Group as an 

a priori critical or important outcome for 

GRADE for vaccine policy decisions

▪ Severe medically-attended RSVassociated LRTI* required at least 1 of the 

following signs/ symptoms:

– Fast breathing (respiratory rate ≥70 (<2 month of 

age [60 days]) or ≥60 (≥2 to 12 months of age) 

breaths per minute

– SpO2 measured in room air <93%

– High-flow nasal cannula or mechanical 

ventilation

– ICU admission for >4 hours

– Unresponsive/unconscious

▪ Included by the Work Group as an a priori

critical outcome for GRADE for vaccine 

policy decisions

▪ Medically-attended RSV-associated LRTI* 

required at least 1 of the following 

signs/symptoms:

– Fast breathing: respiratory rate ≥60 (<2 months 

of age [60 days]) or ≥50 (≥2 to 12 months of age) 

breaths per minute

– SpO2 measured in room air <95%

– Chest wall indrawing

Severe medically attended RSV-associated lower 

respiratory tract infection (LRTI), co-primary trial endpoint

*Medically attended visit includes inpatient and outpatient encounters. Additionally, definition also required RT-PCR or nucleic acid amplification (NAAT) test positive for RSV. Blue text 

denotes differences between the two definitions. SpO2= Peripheral capillary oxygen saturation

1. Kampmann et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants - PubMed (nih.gov)

2. Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document- FDA
18

Phase 3 trial vaccine efficacy against severe medically 

attended RSV-associated LRTI, co-primary trial endpoint

1 Vaccine efficacy was calculated as 1−(P/[1−P]), where P is the number of cases of illness in the RSVpreF group divided by the total number of cases of illness. At 90 days, 99.5% 

confidence intervals (CIs) were used (determined by the alpha-spending function and adjusted with the use of the Bonferroni procedure), and at later intervals, 97.58% CIs were 

used (based on a two-sided alpha level of 0.0483 adjusted with the use of the Bonferroni procedure).

2 Vaccine efficacy was calculated as 1-(hP/[1-P]), where P is the number of cases in the RSVpreF group divided by the total number of cases and h is the ratio of number of 

participants at risk in the placebo group to the number of participants at risk in the RSVpreF group.

1. Kampmann et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants - PubMed (nih.gov)

2.Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document- FDA

Time period 

after birth

Trial dosing interval

(24–36 weeks gestation)

Vaccine efficacy1 (99.5% or 

97.58% CI)

Approved dosing interval 

(32–36 weeks gestation)

Vaccine efficacy2 

(95% CI)

0–90 days 

after birth

81.8% (40.6, 96.3) 91.1% (38.8, 99.8)

0–180 days 

after birth

69.4% (44.3, 84.1) 76.5% (41.3, 92.1)

Within 0-180 days after birth

• Among 81 infants with 

severe medically attended 

RSV LRTI, 50 (62%) were 

hospitalized

• Among 63 infants 

hospitalized with RSV, 50 

(79%) had severe medically 

attended RSV LRTI
19

Effect estimates, harms: Pfizer maternal RSVpreF vaccine 

comparing trial vs approved dosing interval

CI= confidence interval

1 Phase 3 and 2b trials

2 Pooled relative risk estimates were independently calculated using counts of events and participants in the phase 3 trial interim analysis, and phase 2b trial among those who 

received the phase 3 vaccine formulation

Outcome

Trial dosing interval1

(24–36 weeks)

Approved dosing interval1

(32–36 weeks)

Relative Risk2 (95% CI) Relative Risk2 (95% CI)

Harms

Serious adverse events in pregnant people 1.06 (0.95, 1.17) 1.02 (0.87, 1.20)

Reactogenicity (grade 3+) in pregnant people 0.97 (0.72, 1.31) 0.98 (0.62, 1.54)

Serious adverse events in infants 1.01 (0.91, 1.11) 1.04 (0.90, 1.20)

Preterm birth (<37 weeks gestation) 1.20 (0.99, 1.46) 1.15 (0.82, 1.61)
20

Effect estimates, harms: Pfizer maternal RSVpreF vaccine 

comparing trial vs approved dosing interval

CI= confidence interval

1 Phase 3 and 2b trials

2 Pooled relative risk estimates were independently calculated using counts of events and participants in the phase 3 trial interim analysis, and phase 2b trial among those who 

received the phase 3 vaccine formulation

Outcome

Trial dosing interval1

(24–36 weeks)

Approved dosing interval1

(32–36 weeks)

Relative Risk2 (95% CI) Relative Risk2 (95% CI)

Harms

Serious adverse events in pregnant people 1.06 (0.95, 1.17) 1.02 (0.87, 1.20)

Reactogenicity (grade 3+) in pregnant people 0.97 (0.72, 1.31) 0.98 (0.62, 1.54)

Serious adverse events in infants 1.01 (0.91, 1.11) 1.04 (0.90, 1.20)

Preterm birth (<37 weeks gestation) 1.20 (0.99, 1.46) 1.15 (0.82, 1.61)
21

▪ Trial of a similar GSK maternal RSV vaccine (stabilized prefusion F protein vaccine without an adjuvant) 

was halted due to an imbalance of preterm births with higher numbers in the vaccine vs placebo group

▪ Imbalance of neonatal deaths was a consequence of preterm birth imbalance

▪ Imbalance in preterm births was seen in low and middle-income countries (RR: 1.57, 95% CI: 1.17, 2.10) 

but not high-income countries (RR: 1.04, 95% CI: 0.68, 1.58)

▪ Imbalance was observed from April–December 2021, but not consistently after December 2021 

▪ Reason for the imbalance remains unclear

GSK maternal RSV vaccine clinical trial and preterm birth

Study vaccine given at 24 0/7 to 34 0/7 weeks gestation

Vaccines and Related Biological Products Advisory Committee February 28 - March 1, 2023 Meeting Briefing Document- Sponsor GSK (fda.gov)

Outcome Vaccine group, n (%) 

N=3,496

Placebo group, n (%)

N=1,739

Relative Risk (95% CI)

Preterm birth (<37 weeks 

gestation)

238 (6.81%) 86 (4.95%) 1.38 (1.08, 1.75)

Neonatal death 13 (0.37%) 3 (0.17%) 2.16 (0.62, 7.55)
22

Preterm birth in Pfizer RSVpreF vaccine phase 3 trial data, 

comparing trial vs approved dosing interval

Trial dosing interval

(24–36 weeks gestation)1

Approved dosing interval 

(32–36 weeks gestation)1,2

RSVpreF vaccine 

group

N=3,568

Placebo group

N=3,558

RSVpreF vaccine 

group

N=1,628

Placebo group

N=1,604

n % (95% CI) n % (95% CI) n % (95% CI) n % (95% CI)

Preterm birth 

(<37 weeks 

gestation)

202 5.7% 

(4.9%, 6.5%)

169 4.7% 

(4.1%, 5.5%)

68 4.2% 

(3.3%, 5.3%)

59 3.7%

(2.8%, 4.7%)

1. Package Insert -ABRYSVO (STN 125768) (fda.gov)

2. Pfizer response to ACIP, unpublished data, August 2023. In package insert, approved dosing interval reported as: 4.2% (68/1,631) in the RSVpreF group and 3.7% (59/1,610) in 

the placebo group. 
23

Low birth weight and neonatal jaundice outcomes in Pfizer 

RSVpreF vaccine phase 3 trial data, trial vs approved dosing 

interval

Trial dosing interval

(24–36 weeks gestation) 1,2

Approved dosing interval 

(32–36 weeks gestation) 3

RSVpreF vaccine 

group

N=3,568

Placebo group

N=3,558

RSVpreF vaccine 

group

N=1,628

Placebo group

N=1,604

n % (95% CI) n % (95% CI) n % (95% CI) n % (95% CI)

Low birth 

weight 

(≤2500 g)

181 5.1% 

(4.4%, 5.8%)

155 4.4%

(3.7%, 5.1%) 

67 4.1% 

(3.2%, 5.2%)

54 3.4% 

(2.5%, 4.4%)

Neonatal 

jaundice 

257 7.2%

(6.4%, 8.1%)

240 6.7%

(5.9%, 7.6%)

102 6.3%

(5.1%, 7.6%)

107 6.7%

(5.5, 8.0%)

1. Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Presentation- Review of Efficacy and Safety of Respiratory Syncytial Virus Vaccine (ABRYSVO) (fda.gov)

2. Package Insert -ABRYSVO (STN 125768) (fda.gov)

3. Pfizer response to ACIP, unpublished data, August 2023
24

▪ Rate of preterm birth by calendar month of birth

▪ Birth by week of gestational age

▪ Percent of births that were preterm by country

▪ Adverse pregnancy outcomes

In June, ACIP requested additional data regarding the 

Pfizer maternal RSV vaccine
25

Preterm birth rate for vaccine and placebo recipients by 

calendar time—Pfizer Phase 3 trial, trial dosing interval (24–

36 weeks gestation)

GSK signal was present from 

April–December 2021

Data source: Pfizer response to ACIP, unpublished data, July 2023
26

Preterm birth rate for vaccine and placebo recipients by 

calendar time—Pfizer Phase 3 trial, approved dosing 

interval (32–36 weeks gestation)

GSK signal was present from April–

December 2021

Data source: Pfizer response to ACIP, unpublished data, September 2023
27

Number of births by gestational age: Pfizer phase 3 trial, 

trial dosing interval (24–36 weeks gestation)

1 0 1 1 3 1 14 26 29

125

336

764

1262

738

243

20 1 0 1 2 3 1 4 1 0

22 42

93

349

755

1321

680

251

27 2 1

0

200

400

600

800

1000

1200

1400

≥27 to <28 weeks

≥28 to <29 weeks

≥29 to <30 weeks

≥30 to <31 weeks

≥31 to <32 weeks

≥32 to <33 weeks

≥33 to <34 weeks

≥34 to <35 weeks

≥35 to <36 weeks

≥36 to <37 weeks

≥37 to <38 weeks

≥38 to <39 weeks

≥39 to <40 weeks

≥40 to <41 weeks

≥41 to <42 weeks

≥42 to <43 weeks

≥43 to <44 weeks

≥44 to <45 weeks

Number of Births

Gestational Age at Birth

Vaccine Placebo

Preterm birth: <37 weeks gestation

Data source: Pfizer response to ACIP, unpublished data, July 2023
28

Number of births by gestational age, preterm births (<37 

weeks gestation) only: Pfizer phase 3 trial, trial dosing 

interval (24–36 weeks gestation)

1 0 1 1

3 1

14

26 29

125

1 0 1 2 3 1

4

22

42

93

0

20

40

60

80

100

120

≥27 to <28 weeks

≥28 to <29 weeks

≥29 to <30 weeks

≥30 to <31 weeks

≥31 to <32 weeks

≥32 to <33 weeks

≥33 to <34 weeks

≥34 to <35 weeks

≥35 to <36 weeks

≥36 to <37 weeks

Number of Births

Gestational Age at Birth

Vaccine Placebo

Imbalance begins 

at 33 weeks

Preterm birth: <37 weeks gestation

Data source: Pfizer response to ACIP, unpublished data, July 2023
29

Number of births by gestational age: Pfizer phase 3 trial, 

approved dosing interval (32–36 weeks gestation)

Preterm birth: <37 weeks gestation

Data source: Pfizer unpublished data, August 2023

0 2 6 11

49

148

374

567

338

120

12 1 1 5 1

17

35

156

334

603

325

112

14

0

0

100

200

300

400

500

600

≥32 to <33 weeks

≥33 to <34 weeks

≥34 to <35 weeks

≥35 to <36 weeks

≥36 to <37 weeks

≥37 to <38 weeks

≥38 to <39 weeks

≥39 to <40 weeks

≥40 to <41 weeks≥41 to <42 weeks

≥42 to <43 weeks

≥43 to <44 weeks

Number of Births

Gestational Age at Birth

Vaccine Placebo
30

Number of births by gestational age, preterm births (<37 

weeks gestation) only: Pfizer Phase 3 trial, approved 

dosing interval (32–36 weeks gestation)

0

2

6

11

49

1 1

5

17

35

0

5

10

15

20

25

30

35

40

45

50

≥32 to <33 weeks

≥33 to <34 weeks

≥34 to <35 weeks

≥35 to <36 weeks

≥36 to <37 weeks

Number of Births

Gestational Age at Birth

Vaccine Placebo

Preterm birth: <37 weeks gestation

Data source: Pfizer unpublished data, August 2023
31

Number births and percent preterm by country–Pfizer phase 3 trial

Trial dosing interval (24–36 weeks gestation) Approved dosing interval (32–36 weeks gestation)

RSVpreF recipients

N=3568

Placebo recipients

N=3558

RSVpreF recipients

N=1628

Placebo recipients

N=1604

Country No. births % preterm No. births % preterm No. births % preterm No. births % preterm

Argentina 423 6.4% 416 4.1% 230 4.8% 230 4.3%

Australia 11 0.0% 13 7.7% 8 0.0% 8 12.5%

Brazil 35 8.6% 37 2.7% 22 9.1% 23 4.3%

Canada 27 0.0% 28 3.6% 20 0.0% 27 3.7%

Chile 86 8.1% 85 7.1% 47 6.4% 50 2.0%

Denmark 30 3.3% 31 0.0% 21 4.8% 17 0.0%

Finland 75 2.7% 73 1.4% 44 0.0% 40 2.5%

Gambia 78 2.6% 79 2.5% 32 3.1% 24 0.0%

Japan 218 3.2% 216 6.0% 111 2.7% 94 2.1%

Korea 7 0.0% 4 25.0% 6 0.0% 1 100.0%

Mexico 37 8.1% 37 5.4% 13 7.7% 13 0.0%

Netherlands 97 3.1% 95 3.2% 43 2.3% 44 0.0%

New Zealand 49 4.1% 47 6.4% 29 3.4% 28 3.6%

Philippines 32 3.1% 34 5.9% 0 0.0% 1 0.0%

South Africa 469 8.3% 471 4.0% 150 6.7% 127 2.4%

Spain 117 3.4% 123 2.4% 73 2.7% 88 3.4%

Taiwan 123 4.9% 125 5.6% 58 5.2% 57 3.5%

United States 1654 5.7% 1644 5.3% 721 4.0% 732 4.4%

Data source: Pfizer response to ACIP, unpublished data, July and August 2023. Trial included 480 sites across 18 countries. Number of births is the total number of births regardless of gestational age. 

Blue indicates higher percent of preterm birth among RSVpreF vs. placebo in trial dosing interval, red in approved dosing interval, and purple in both dosing intervals. Black indicates either balanced 

preterm birth rates or a higher percent of preterm births among placebo vs RSVpreF recipients. Caution should be used in interpreting rates based on small numbers; some differ by very small counts. 
32

Number births and percent preterm by country–Pfizer phase 3 trial

Trial dosing interval (24–36 weeks gestation) Approved dosing interval (32–36 weeks gestation)

RSVpreF recipients

N=3568

Placebo recipients

N=3558

RSVpreF recipients

N=1628

Placebo recipients

N=1604

Country No. births % preterm No. births % preterm No. births % preterm No. births % preterm

Argentina 423 6.4% 416 4.1% 230 4.8% 230 4.3%

Australia 11 0.0% 13 7.7% 8 0.0% 8 12.5%

Brazil 35 8.6% 37 2.7% 22 9.1% 23 4.3%

Canada 27 0.0% 28 3.6% 20 0.0% 27 3.7%

Chile 86 8.1% 85 7.1% 47 6.4% 50 2.0%

Denmark 30 3.3% 31 0.0% 21 4.8% 17 0.0%

Finland 75 2.7% 73 1.4% 44 0.0% 40 2.5%

Gambia 78 2.6% 79 2.5% 32 3.1% 24 0.0%

Japan 218 3.2% 216 6.0% 111 2.7% 94 2.1%

Korea 7 0.0% 4 25.0% 6 0.0% 1 100.0%

Mexico 37 8.1% 37 5.4% 13 7.7% 13 0.0%

Netherlands 97 3.1% 95 3.2% 43 2.3% 44 0.0%

New Zealand 49 4.1% 47 6.4% 29 3.4% 28 3.6%

Philippines 32 3.1% 34 5.9% 0 0.0% 1 0.0%

South Africa 469 8.3% 471 4.0% 150 6.7% 127 2.4%

Spain 117 3.4% 123 2.4% 73 2.7% 88 3.4%

Taiwan 123 4.9% 125 5.6% 58 5.2% 57 3.5%

United States 1654 5.7% 1644 5.3% 721 4.0% 732 4.4%

Data source: Pfizer response to ACIP, unpublished data, July and August 2023. Trial included 480 sites across 18 countries. Number of births is the total number of births regardless of gestational age. 

Blue indicates higher percent of preterm birth among RSVpreF vs. placebo in trial dosing interval, red in approved dosing interval, and purple in both dosing intervals. Black indicates either balanced 

preterm birth rates or a higher percent of preterm births among placebo vs RSVpreF recipients. Caution should be used in interpreting rates based on small numbers; some differ by very small counts. 
33

Select pregnancy-related serious adverse events at any 

time following vaccination1,2: Pfizer phase 3 trial, trial 

dosing interval (24–36 weeks gestation)

1 Table 3 ABRYSVO package insert Package Insert -ABRYSVO (STN 125768) (fda.gov)

2 Includes all SAEs from vaccination to 6 months post-delivery (up to approximately 10 months, depending on the gestational age at the time of vaccination). In the phase 3 RCT, 

eclampsia occurred in 5 participants (3 in the RSVpreF group and 2 in the placebo group) and HELLP syndrome occurred in 5 participants (2 in the RSVpreF group and 3 in the 

placebo group).

3 There was one maternal death in the vaccine group due to postpartum hemorrhage that was not likely to be associated with vaccination.

4 A total of 18 intrauterine deaths were reported for the index pregnancy: 10 intrauterine deaths in the vaccine group (0.3%) and 8 intrauterine deaths in the placebo group 

(0.2%). The intrauterine deaths represented various clinical conditions and presentations resulting in fetal demise without clear evidence of a common pathophysiology.

RSVpreF Vaccine 

N= 3,682

Placebo

N= 3,675

Serious Adverse Reaction n (%) 95% CI n (%) 95% CI

All Maternal Serious Adverse Events (SAEs) 598 (16.2) (15.1, 17.5) 558 (15.2) (14.0, 16.4)

Pre-eclampsia 68 (1.8) (1.4, 2.3) 53 (1.4) (1.1, 1.9)

Gestational hypertension 41 (1.1) (0.8, 1.5) 38 (1.0) (0.7, 1.4)

Premature rupture of membranes 15 (0.4) (0.2, 0.7) 16 (0.4) (0.2, 0.7)

Preterm premature rupture of membranes 15 (0.4) (0.2, 0.7) 10 (0.3) (0.1, 0.5)

Hypertension 13 (0.4) (0.2, 0.6) 6 (0.2) (0.1, 0.4)

Maternal death3 1 (<0.1) (0.0, 0.2) 0 (0.0, 0.1)

Fetal death4 10 (0.3) (0.1, 0.5) 8 (0.2) (0.1, 0.4)
34

▪ Same Pfizer RSV vaccine, formulation and dose approved for use in adults ages 60 

years and older

▪ Within the trials for this product among adults ages 60 years and older, a potential

safety signal of inflammatory neurologic events was identified

▪ A total of 3 cases of interest were recorded among 20,255 investigational vaccine 

recipients aged 60 years and older. No cases were observed among placebo 

recipients.

– 1 case of Guillain-Barré Syndrome (GBS)

– 1 case of Miller Fisher syndrome (a GBS variant)

– 1 case of undifferentiated motor-sensory axonal polyneuropathy (with 

worsening of preexisting symptoms)

Other considerations: Inflammatory neurologic events and 

Pfizer RSVpreF Vaccine 

Melgar et al. Use of Respiratory Syncytial Virus Vaccines in Older Adults: Recommendations of the Advisory Committee on Immunization Practices — United States, 2023 | 

MMWR (cdc.gov)
35

▪ No Guillain-Barré syndrome (GBS) or other demyelinating events were 

reported in the phase 2b or 3 trials among pregnant people1

▪ Background rate of GBS in pregnant people is much lower than among 

older adults2,3

▪ Incidence rate of GBS in pregnant people in the Vaccine Safety Datalink 

during 2004–2015: 2.8 (95% CI 0.5–9.3) per million person-years (based on 

2 cases)2

Other considerations: Inflammatory neurologic events and 

Pfizer RSVpreF Vaccine (cont.)

1. Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document- FDA

2. Myers TR, McCarthy NL, Panagiotakopoulos L, Omer SB. Estimation of the Incidence of Guillain-Barré Syndrome During Pregnancy in the United States. Open Forum Infect Dis. 

2019 Mar 15;6(3):ofz071. doi: 10.1093/ofid/ofz071. 

3. Sejvar JJ, Baughman AL, Wise M, Morgan O. Population Incidence of Guillain-Barré Syndrome: A Systematic Review and Meta-Analysis. Neuroepidemiology 2011;36:123–133 
36

▪ Efficacious vaccine that can prevent RSV lower respiratory tract 

infection in young infants

▪No consensus among Work Group regarding clinical importance 

of preterm birth imbalance observed in clinical trials

Summary of Benefits and Harms
37

▪ Though not statistically significant, imbalance in preterm births was seen in the full 

trial population

▪ Trial powered for efficacy outcomes and not designed or powered to detect 20% 

increase in preterm birth

▪ There may have been less precise dating of gestational age in some sites and 

countries in the trial, but there is no reason this should bias towards a preterm birth 

imbalance among vaccinated compared to placebo participants

▪ Preterm birth signal in the GSK maternal RSV vaccine trial (also a stabilized prefusion 

F protein vaccine) adds to concern

Work Group members found the following points 

concerning regarding preterm birth
38

▪ When using the full trial dosing interval (24–36 weeks gestation), most preterm births (60%) 

were >30 days after vaccination, and no known biologic mechanism for vaccines to cause 

preterm birth, particularly >30 days after vaccination

▪ When assessed among those vaccinated during the approved interval (32–36 weeks 

gestation), data on preterm birth were reassuring to the Work Group

– Imbalance in preterm birth was still present but lessened

– Most infants born preterm in the vaccine group (72%, 49/68) were born at 36 weeks

– In the United States (largest contributing country in the trial), imbalance in preterm births 

reversed: 

• Trial dosing interval: 5.7% in vaccine vs. 5.3% in placebo recipients

• Approved dosing interval: 4.0% in vaccine vs. 4.4% in placebo recipients 

▪ Majority of the Work Group felt the approved dosing interval (32–36 weeks gestation) reduces 

the potential risk of preterm birth and the potential for complications from preterm birth, 

which is their major safety concern

Work Group members found the following data reassuring 

regarding preterm birth imbalance
39

▪How substantial are the desirable anticipated effects?

–How substantial are the anticipated effects for:

• Medically attended RSV-associated lower respiratory infection in infants 

• Hospitalization for RSV-associated lower respiratory tract infection in infants 

• ICU admission from RSV hospitalization in infants 

• Mechanical ventilation from RSV hospitalization in infants 

• RSV-associated death in infants 

• All-cause hospitalization for lower respiratory tract infection in infants 

• All-cause medically attended lower respiratory tract infection in infants 

Benefits and Harms - Pfizer maternal RSVpreF vaccine, 

given as a single dose at 32–36 weeks gestation

Minimal Small Moderate Large Varies Don’t know

Majority Opinion Minority Opinion

0
40

▪How substantial are the undesirable anticipated effects?

–How substantial are the anticipated effects for:

• Serious adverse events in pregnant people 

• Reactogenicity (3+ or higher) in pregnant people 

• Serious adverse events in infants 

• Preterm birth 

Benefits and Harms - Pfizer maternal RSVpreF vaccine, 

given as a single dose at 32–36 weeks gestation

Minimal Small Moderate Large Varies Don’t know

Majority Opinion
41

▪Do the desirable effects outweigh the undesirable effects?

–What is the balance between the desirable effects relative to the 

undesirable effects?

Benefits and Harms - Pfizer maternal RSVpreF vaccine, 

given as a single dose at 32–36 weeks gestation

Favors intervention (Pfizer Maternal RSVpreF 

Vaccine)

Favors comparison (No intervention)

Favors both

Favors neither

Unclear

0

Majority Opinion
42

EtR Domain: Values

Criterion 1: Does the target population feel that the 

desirable effects are large relative to undesirable effects? 

Criterion 2: Is there important uncertainty about, or 

variability in, how much people value the main 

outcomes?
43

▪ Values survey of pregnant and recently pregnant people conducted from December 

21, 2022–January 2, 2023 by University of Iowa, RAND, and CDC1

– 68% of respondents had knowledge of RSV prior to taking survey

– 61% of respondents said they ‘definitely’ or ‘probably’ would get an RSV vaccine while pregnant

– Among those who did not respond that they “definitely would” get an RSV vaccine while pregnant, safety 

concerns, lack of RSV knowledge, and concerns about vaccination causing or intensifying RSV infection 

were the top reasons for not wanting an RSV vaccine during pregnancy

▪ In the US, coverage for recommended vaccines among pregnant people has decreased 

during the pandemic and varies by race and ethnicity2

– Tdap vaccination coverage was 53.5% in 2020–21 season and 45.8% in 2021–22 season

– Rates of Tdap coverage were higher in White, non-Hispanic women than among Black, non-Hispanic women 

during the 2020–21 and 2021–22 seasons

Summary of values domain

1 CDC and University of Iowa/RAND survey, unpublished

2 Flu, Tdap, and COVID-19 Vaccination Coverage Among Pregnant Women – United States, April 2022 | FluVaxView | Seasonal Influenza (Flu) | CDC
44

▪Criterion 1: Do pregnant people feel that the desirable effects 

are large relative to undesirable effects?

Values

No Probably No Probably Yes Yes Varies Don’t know

Majority Opinion
45

▪Criterion 2: Is there important uncertainty about, or variability in, 

how much pregnant people value the main outcomes?

Values

Important uncertainty or variability

Probably important uncertainty or variability

Probably not important uncertainty or variability

No important uncertainty or variability

No known undesirable outcomes

Most common answers
46

EtR Domain: Acceptability

Is the intervention acceptable to key stakeholders?
47

▪ Obstetrician and midwife support of RSV vaccine, if it was routinely 

recommended:

– 47% definitely

– 34% likely

– 14% not sure

– 4% unlikely

– 0.5% very unlikely

Maternity healthcare professionals survey—England, 2019

Wilcox CR, Calvert A, Metz J, et al. Attitudes of Pregnant Women and Healthcare Professionals Toward Clinical Trials and Routine Implementation of Antenatal Vaccination Against 

Respiratory Syncytial Virus: A Multicenter Questionnaire Study. The Pediatric Infectious Disease Journal. 2019 Sept;38(9):944-951. DOI: 10.1097/INF.0000000000002384
48

▪ Is RSV prevention with Pfizer maternal RSVpreF vaccine 

acceptable to key stakeholders?

Acceptability

No Probably No Probably Yes Yes Varies Don’t know

Majority Opinion Minority Opinion
49

EtR Domain: Feasibility

Is the intervention feasible to implement?
50

▪ Storage and handling requirements

– Supplied as single 0.5 mL dose, or as a 5-pack or 10-pack of single-dose kits 

– Reconstitution required: single dose vial of lyophilized powder, reconstitution 

supplies included in kit 

– Product should be refrigerated (2–8°C) in original container, protected from light 

– After reconstitution, the product should be administered within 4 hours, otherwise 

discarded

▪ Most pregnant patients receive Tdap vaccine in an obstetrician's or midwife’s office

– Likely pregnant patients would also most often receive RSV vaccine at their prenatal 

care provider’s office

Storage and handling

Package Insert -ABRYSVO (STN 125769/26) (fda.gov) 

Flu, Tdap, and COVID-19 Vaccination Coverage Among Pregnant Women –United States, April 2022 | FluVaxView | Seasonal Influenza (Flu) | CDC
51

▪ Pregnant people may potentially be eligible to receive RSV, Tdap, COVID-19, and 

influenza vaccines at same visit

▪ Pfizer Phase 2b study in healthy non-pregnant women ages 18–49 years on 

simultaneous administration of Tdap and Pfizer RSVpreF found decreased immune 

response to pertussis components (i.e., non-inferiority criteria were not met)1

▪ Given lack of correlates of protection for pertussis, it is unclear how this might impact 

protection against pertussis from maternal Tdap when simultaneously administered 

with RSVpreF vaccine

Simultaneous administration of RSV vaccine with other 

vaccines in pregnant people

1 Peterson et al. Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F Vaccine When CoadministeredWith a Tetanus, Diphtheria, and Acellular Pertussis 

Vaccine.The Journal of Infectious Diseases. 2022 June 15; 225(12): 2077–2086. doi: 10.1093/infdis/jiab505
52

▪ Tdap recommended every pregnancy, preferably during the early part of gestational 

weeks 27 through 361

▪ Tdap would be preferably given before 32 weeks (based on recommendation) and RSV 

vaccine would be given at or after 32 weeks

▪ In MarketScan data from 2018–2021, about half of captured Tdap doses were given 

before 32 weeks gestation2

RSV vaccine and Tdap dosing timing

1 CDC, https://www.cdc.gov/vaccines/vpd/dtap-tdap-td/hcp/recommendations.html

2 MarketScan data, 2018-2021
53

▪ Either RSV vaccination during pregnancy or nirsevimab administration for the infant 

can be used to prevent RSV lower respiratory tract infection in infants

▪ Work Group felt both products are not needed for most infants

▪ Pregnant person and prenatal care provider will need to make the decision during 

pregnancy regarding which RSV prevention product to use

▪ Many prenatal care providers may not have time to discuss options for RSV prevention 

with their patients

▪ Prenatal care providers may not feel equipped to discuss nirsevimab, as this product 

will be given to the infant after birth

RSVpreF vaccine is one of two available preventive 

products for RSV in infants
54

▪ Maximizes cost-effectiveness

▪ Maximizes benefits for infants 

▪ Targets dosing to infants who will be in the first months of life during RSV season

▪ Another product (nirsevimab) is available for infants who are born out of season— for 

whom maternal vaccine protection would have waned by RSV season

Work Group unanimously supported use of a seasonal 

dosing strategy for maternal RSV vaccine
55

▪ Work Group supported seasonal dosing during September through January in most 

of the continental US based on typical (pre-pandemic) RSV seasonality

– Aligns with implementation of influenza vaccine and thus would simplify 

implementation for prenatal care providers 

▪ Work Group felt that jurisdictions in which RSV seasonality differs from most of the 

continental US should have flexibility regarding start and stop of administration of 

RSVpreF vaccine in pregnant people

• Alaska

• Tropical climates: parts of Florida, Puerto Rico, U.S. Virgin Islands, Hawaii, Guam, 

and U.S.-affiliated Pacific Islands

Seasonal dosing for RSVpreF vaccine
56

▪ Is Pfizer Maternal RSVpreF vaccine feasible to implement among 

pregnant people at 32–36 weeks gestation?

Feasibility

No Probably No Probably Yes Yes Varies Don’t know

Majority Opinion Minority Opinion
57

EtR Domain: Resource Use

Is the intervention a reasonable and efficient allocation of 

resources?
58

Scenarios for cost-effectiveness by months of RSVpreF

vaccine dosing during the calendar year

ICER: Incremental cost-effectiveness ratio

QALY: Quality-Adjusted Life-Year

Cost-effectiveness model assumes typical RSV seasonality (based on pre-pandemic years) in most of the continental United States.

$400,304 

$363,344 

$322,594 

$282,498 

$186,256 $167,280 $141,806 

 $-

 $50,000

 $100,000

 $150,000

 $200,000

 $250,000

 $300,000

 $350,000

 $400,000

 $450,000

Base Apr-Feb May-Feb Jun-Feb Aug-Jan Sep-Jan Sep-Dec

ICER ($.QALY)

Months of RSV vaccine dosing

ICER: RSVpreF vs. Natural History
59

▪ RSVpreF vaccine may improve RSV outcomes but will also increase costs

– Base case incremental cost-effectiveness (ICER) ratio : $400,304/QALY

• Year-round dosing 

• Typical RSV seasonality (based on pre-pandemic years) in most of the continental United 

States

– Work group felt that this vaccine would not be cost-effective under the base case conditions

▪ Cost-effectiveness would improved by using a seasonal dosing strategy

– September through January in most of the continental US based on typical (pre-pandemic) 

RSV seasonality

▪ Work Group unanimously supported use of a seasonal dosing strategy

WG interpretations: Resource Use

QALY: Quality-Adjusted Life-Year

Cost-effectiveness model assumes typical RSV seasonality (based on pre-pandemic years) in most of the continental United States.
60

▪ Is Pfizer Maternal RSVpreF vaccine use among pregnant people 

at 32–36 weeks gestation a reasonable and efficient allocation of 

resources?

▪ Work Group responses were based on seasonal dosing for RSVpreF vaccine (i.e., 

September-January in most of the continental United States)

Resource Use

No Probably No Probably Yes Yes Varies Don’t know

Majority Opinion Minority Opinion
61

EtR Domain: Equity

What would be the impact of the intervention on health equity?
62

▪ National studies of death certificates found higher rates of RSVassociated deaths among non-Hispanic Black children compared with 

non-Hispanic White infants and children aged 1–4 years1

▪ ICU admission rates for RSV among Non-Hispanic Black infants <6 

months old were 1.2–1.6x higher than among Non-Hispanic White infants2

▪ RSV hospitalization rates 4–10x higher among Alaska Native and 

American Indian children ages <24 months than the rate in the general 

population3 

– This study was limited to specific populations and might not be broadly 

representative of risk in all Alaska Native and American Indian children

Equity summary: Incidence of RSV disease by race and 

ethnicity in infants and children

1. Hansen et al. The Use of Death Certificate Data to Characterize Mortality Associated With Respiratory Syncytial Virus, Unspecified Bronchiolitis, and Influenza in the United 

States, 1999-2018 J Infect Dis. 2022 Aug 15;226(Supplement 2): S255–S266.

2 Unpublished data from RSV-NET, CDC. 

3 Atwell et al. RSV Among American Indian and Alaska Native Children: 2019 to 2020 Pediatrics. 2023 Aug 1;152(2):e2022060435
63

▪ By federal law, all states provide Medicaid coverage for pregnancy-related services to 

pregnant women with incomes up to 138% of the federal poverty level1

▪ In 2021, 41.0% of mothers had Medicaid at the time of birth2

▪ If recommended, ACIP will vote on a Vaccines for Children resolution for the Pfizer 

RSV vaccine for pregnant people <19 years of age

▪ After October 1, 2023, when the Inflation Reduction Act provisions become effective, 

state Medicaid agencies will be required to cover vaccines and their administration 

without cost-sharing for nearly all full-benefit adult beneficiaries covered under 

traditional Medicaid, if the CDC/ACIP recommendations apply

Equity summary: Medicaid coverage for pregnant people 

and vaccines during pregnancy

1 Medicaid Coverage for Women | KFF

2 2023 Medicaid and CHIP Beneficiary Profile: Enrollment, Expenditures, Characteristics, Health Status, and Experience
64

▪ Under the Affordable Care Act and its implementing regulations, ACIP 

recommendations that have been adopted by CDC “with respect to the individual 

involved” and are “listed on the Immunization Schedules of the Centers for Disease 

Control and Prevention” generally are required to be covered by group health plans 

and health insurance issuers offering group or individual health insurance coverage 

without imposing any cost-sharing requirements (such as a copayment, coinsurance, 

or deductible)

Equity summary: Other insurance coverage for vaccines 

during pregnancy

ACIP Shared Clinical Decision-Making Recommendations | CDC
65

▪What would be the impact of Pfizer Maternal RSVpreF vaccine 

on health equity? Answers ranged, no majority

Equity

Reduced

Probably reduced

Probably no impact

Probably increased

Increased

Varies

Don’t know

2 Most common nd most common 3rd most common
66

Summary
67

Evidence to Recommendations (EtR) framework

EtR Domain Question(s) Work Group Judgements

Public Health Problem Is the problem of public health importance? Yes

Benefits and Harms How substantial are the desirable anticipated effects? Large

How substantial are the undesirable anticipated effects? Small

Do the desirable effects outweigh the undesirable effects? Favors intervention

Values Does the target population feel the desirable effects are large 

relative to the undesirable effects?

Probably yes

Is there important uncertainty about, or variability in, how 

much people value the main outcomes?

Probably not important 

uncertainty or variability/ 

Probably important 

uncertainty or variability

Acceptability Is the intervention acceptable to key stakeholders? Yes

Feasibility Is the intervention feasible to implement? Yes

Resource Use Is the intervention a reasonable and efficient allocation of 

resources?

Probably yes, with seasonal 

dosing

Equity What would be the impact of the intervention on health 

equity?

Ranged from probably no 

impact to increased
68

Evidence to Recommendations framework 

Summary: Work Group interpretations

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

Majority Opinion Minority Opinion
69

Evidence to Recommendations framework

Summary: Work Group interpretations

Type of 

Recommendation

We do not 

recommend the 

intervention

We recommend the 

intervention for 

individuals based on 

shared clinical 

decision-making

We recommend the 

intervention

Majority Opinion Minority Opinion
70

▪ Majority of Work Group was supportive of intervention with Pfizer maternal RSVpreF 

vaccine for pregnant people with dosing during the approved dosing interval (32–36 

weeks gestation) 

– Found the data on preterm birth when assessed among those vaccinated during the 

approved dosing interval (32–36 weeks gestation) to be reassuring 

– Felt the approved dosing interval (32–36 weeks gestation) reduces the potential risk 

of preterm birth and the potential for complications from preterm birth, which is 

their major safety concern

▪ All Work Group members endorsed the importance of post-introduction vaccine safety 

monitoring

Work Group considerations: Benefit and harms
71

▪ Unanimously supported use of a seasonal dosing strategy which would maximize 

benefits and cost-effectiveness 

▪ Supported that RSVpreF vaccine dosing should occur during September–January in 

most of the continental United States 

▪ Felt that jurisdictions in which RSV seasonality differs from most of the continental US 

should have flexibility regarding start and stop of administration of RSVpreF vaccine in 

pregnant people

Work Group considerations: Seasonal dosing
72

▪ Pregnant people should have options for RSV prevention

– Nirsevimab may not be readily available in all settings 

– Pregnant people and their providers may have preferences regarding these two 

products

▪ Pregnant people should be made aware that they can either receive RSVpreF vaccine 

during pregnancy or nirsevimab can be given to the infant, but most infants will not 

need both

▪ Pregnant people should be informed regarding the risks and benefits of both products 

before making a decision

Work Group considerations: RSVpreF vaccine is one of two 

available preventive products for RSV in infants
73

▪ Most work group members support a full recommendation

– Approved dosing interval (32–36 weeks) reduces the potential risk of and complications from preterm birth

– Importance of clear vaccine recommendations

– Providers who will help pregnant people decide which product to receive generally have less familiarity with the 

data than ACIP

– SCDM can be confusing to providers, hard to implement for providers, can lead to lower vaccine confidence and 

uptake of vaccination, and could potentially influence support for the vaccine in lower and middle income 

countries

▪ Minority supported a recommendation with SCDM 

– Without SCDM, a full recommendation could result in some providers recommending RSVpreF vaccine during 

pregnancy without discussing with pregnant patients that nirsevimab is an option

– Potential risk for preterm birth (and neuroinflammatory events)

– Same vaccine is recommended under SCDM for adults ages 60 years and older

▪ ACIP generally makes SCDM recommendations when individuals may benefit from 

vaccination, but broad vaccination of people in that group is unlikely to have 

population-level impacts

Work Group considerations: Full vs shared clinical decision making 

(SCDM) recommendation for Pfizer maternal RSVpreF vaccine during 

the approved dosing interval (32–36 weeks gestation)
74

▪ Currently there are no data available on:

– Efficacy of the first lifetime dose during subsequent pregnancies

– Safety of additional doses given in subsequent pregnancies

▪ Work Group felt that it was too early to decide whether additional doses should be 

given in subsequent pregnancies given the lack of data

▪ Additional data are needed to inform whether additional doses in subsequent 

pregnancies would be indicated, and recommendations can be updated in the future

Work Group considerations: Additional vaccine doses in 

subsequent pregnancies
75

▪ Maternal RSV vaccine is recommended for pregnant people during 32 

through 36 weeks gestation, using seasonal administration, to prevent 

RSV lower respiratory tract infection in infants

Proposed voting language
76

Jefferson Jones

Lauren Roper 

Meredith McMorrow 

Mila Prill 

Monica Godfrey 

Michael Melgar

Amadea Britton

Amanda Payne 

Megan Wallace

Danielle Moulia

Morgan Najdowski 

David Hutton 

Jamison Pike 

Andrew Leidner 

Ismael Ortega-Sanchez 

Karen Broder

Naomi Tepper

Heidi Moline

Amber Winn

Monica Patton

Jenny Milucky

Fiona Havers 

Rebecca Morgan 

Doug Campos-Outcalt

Patricia Wodi

Sascha Ellington

Megan Lindley

Fangjun Zhou

Sarah Meyer

David Hutton

Barbara Mahon

Aron Hall

Coronavirus and Other 

Respiratory Viruses Division

Immunization Services 

Division 

Acknowledgements 
77

▪ We acknowledge that not every person who can become pregnant identifies as a 

woman. Although we try to use gender-neutral language as often as possible, much of 

the research available currently refers only to “women” when discussing the ability to 

become pregnant. When citing research, we refer to the language used in the study. In 

these cases, “woman” refers to someone who was assigned female at birth. For clarity 

in terminology, “maternal” is used to identify the person who is pregnant or 

postpartum throughout this presentation; the authors are aware that pregnancy is not 

equated with the decision to parent nor do all parents who give birth identify as 

mothers.

Note
78

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.
79

Centers for Disease Control and Prevention

National Center for Immunization and Respiratory Diseases

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Grading of Recommendations, Assessment, Development, 

and Evaluation (GRADE): 

Pfizer Maternal RSVpreF Vaccine 

Update: September 6, 2023
80

Evidence Retrieval, conducted as of April 10, 2023

*Medline (OVID), Embase (OVID), Cochrane Library, CINAHL (EbscoHost), Scopus, clinicaltrials.gov

Records screened*

(n=161) Duplicates removed

(n=7)

Studies irrelevant

(n=139) Full text studies 

assessed for 

eligibility

(n=12)

Studies excluded

(n=10)

7 wrong intervention

3 wrong patient population

Records included 

in evidence 

synthesis 

(n=2)
81

▪ High certainty: We are very confident that the true effect lies close to that of the 

estimate of the effect.

▪ Moderate certainty: We are moderately confident in the effect estimate: The true 

effect is likely to be close to the estimate of the effect, but there is a possibility that it 

is substantially different.

▪ Low certainty: Our confidence in the effect estimate is limited: The true effect may be 

substantially different from the effect estimate.

▪ Very low certainty: We have very little confidence in the effect estimate: The true 

effect is likely to be substantially different from the estimate of the effect.

GRADE Evidence Type

NOTE: Evidence type is not measuring the quality of individual studies, but how much certainty we 

have in the estimates of effect across each outcome.
82

▪ Initial evidence type (certainty level) determined by study design

– Initial evidence high certainty: A body of evidence from randomized 

controlled trials

– Initial evidence low certainty: A body of evidence from observational 

studies

▪ The certainty of evidence may be downgraded due to risk of bias, 

inconsistency, indirectness, imprecision, or publication bias. For nonrandomized studies, the certainty may be rated up for presence of doseresponse gradient, large or very large magnitude of effect, and opposing 

residual confounding.

GRADE Evidence Type

NOTE: Evidence type is not measuring the quality of individual studies, but how much certainty we 

have in the estimates of effect across each outcome.
83

Benefits
84

Vaccine efficacy methods

*8 participants (3 in the vaccine group and 5 in the placebo group) received injection at >36 weeks gestation and were included in the analysis

Dosing interval Number of 

Participants

VE Formula Outcomes Reference

Phase 3 trial, Trial 

dosing interval 

(24–36 weeks)*

Vaccine: 3495

Placebo: 3480

1–(P/[1–P]), where P is the number of 

cases in the RSVpreF group divided by 

the total number of cases

• Medically attended RSV-associated lower 

respiratory tract infection in infants

• Hospitalization for RSV-associated lower 

respiratory tract infection in infants

• All-cause medically attended lower 

respiratory tract infection in infants 

Kampmann et al. and 

VRBPAC briefing 

document

Phase 3 trial, Trial 

dosing interval 

(24–36 weeks)*

Vaccine: 3495

Placebo: 3480

1–(P/[1–P]), where P is the number of 

cases in the RSVpreF group divided by 

the total number of cases

• ICU admission from RSV hospitalization in 

infants

• Mechanical ventilation from RSV 

hospitalization in infants

• All-cause hospitalization for lower 

respiratory tract infection in infants 

Post-hoc analysis, 

data provided by the 

manufacturer for 

GRADE

Phase 3 trial, 

Approved dosing 

interval (32–36 

weeks) 

Vaccine: 1572

Placebo: 1539

1-(hP/[1-P]), where P is the number of 

cases in the RSVpreF group divided by 

the total number of cases and h is the 

ratio of number of participants at risk in 

the placebo group to the number of 

participants at risk in the RSVpreF group

All efficacy outcomes Post-hoc analysis, 

data provided by the 

manufacturer
85

▪ Pfizer phase 3 randomized controlled trial (RCT), MATISSE1

▪ Trial locations: Argentina, Australia, Brazil, Canada, Chile, Denmark, Finland, Gambia, Japan, Republic of 

Korea, Mexico, Netherlands, New Zealand, Philippines, South Africa, Spain, Taiwan, United States

– 45% of participants from United States

▪ Study enrollment and efficacy follow-up occurred June 17, 2020, to October 2, 2022

▪ Data evaluated: data cut-off September 30, 2022; mean follow-up in infant participants 11.97 months 

after birth (range: 0.0, 24.3)

▪ Infant evaluable efficacy set: 3,495 in vaccine arm; 3,480 in placebo arm

▪ Exclusion criteria of certain conditions may not represent all pregnant people and their infants in the 

United States 

▪ Placebo was not a saline placebo, but a lyophile match to the vaccine consisting of excipients matched 

to those used in the RSVpreF vaccine formulation, minus the active ingredients

Outcome 1: Medically attended RSV-associated lower 

respiratory tract infection in infants (n=1 study)

1 Kampmann B, Madhi SA, Munjal I, et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants. N Engl J Med. 2023 Apr 5. doi: 10.1056/NEJMoa2216480.
86

▪ Medically attended visit (inclusive of inpatient and outpatient encounters) 

and ≥1:

– Fast breathing: respiratory rate ≥60 bpm (<2 months of age [60 days]) or 

≥50 bpm (≥2 to 12 months of age)

– SpO2 measured in room air <95%

– Chest wall indrawing

▪ RSV RT-PCR–positive test result by Pfizer central laboratory or by 

certified laboratory with NAAT for RSV 

▪ Confirmed by endpoint adjudication committee (EAC)

Outcome 1: Medically attended RSV-associated lower 

respiratory tract infection in infants (n=1 study)
87

Outcome 1: Medically attended RSV-associated lower 

respiratory tract infection in infants (n=1 study)

RR= relative risk, CI=confidence interval

1 Vaccine efficacy was calculated as 1−(P/[1−P]), where P is the number of cases of illness in the RSVpreF group divided by the total number of cases of illness. At 90 days, 99.5% 

confidence intervals (CIs) were used (determined by the alpha-spending function and adjusted with the use of the Bonferroni procedure), and at later intervals, 97.58% CIs were 

used (based on a two-sided alpha level of 0.0483 adjusted with the use of the Bonferroni procedure). Efficacy is from full phase 3 trial data, using trial dosing interval (24–36 weeks 

gestation).

2 This outcome did not meet success criterion using manufacturer calculated VE (lower bound of CI was <20%) 

Time period 

after birth

Events/Vaccine

(n/N)

Events/Placebo

(n/N)

Vaccine efficacy (1 – RR)

(95% CI)

Manufacturer calculated 

vaccine efficacy1 (99.5% 

or 97.58% CI)

0–90 days after 

birth2

24/3495 56/3480 57.3% (31.3, 73.5) 57.1% (14.7, 79.8)

0–120 days after 

birth

35/3495 81/3480 57.0% (36.2, 71.0) 56.8% (31.2, 73.5)

0–150 days after 

birth

47/3495 99/3480 52.7% (33.3, 66.5) 52.5% (28.7, 68.9)

0–180 days after 

birth

57/3495 117/3480 51.5% (33.7, 64.5) 51.3% (29.4, 66.8)
88

▪ Medically attended visit (inclusive of inpatient and outpatient encounters) 

and ≥1:

– Fast breathing (respiratory rate ≥70 (<2 month of age [60 days]) or ≥60 (≥2 

to 12 months of age)

– SpO2 measured in room air <93%

–High-flow nasal cannula or mechanical ventilation

– ICU admission for >4 hours

–Unresponsive/unconscious

▪ RSV RT-PCR–positive test result by Pfizer central laboratory or by 

certified laboratory with NAAT for RSV 

▪ Confirmed by EAC

Outcome 1: Severe medically attended RSV-associated 

lower respiratory tract infection in infants (n=1 study)

SpO2= Peripheral capillary oxygen saturation; RT-PCR = Real-time polymerase chain reaction; NAAT= nucleic acid amplification technology; EAC= endpoint adjudication committee

Blue text denotes differences between definitions of severe medically attended RSV-associated lower respiratory tract infection and medically attended RSV-associated lower 

respiratory tract infection.
89

Outcome 1: Severe medically attended RSV-associated 

lower respiratory tract infection in infants (n=1 study)

RR= relative risk, CI= confidence interval

1 Vaccine efficacy was calculated as 1−(P/[1−P]), where P is the number of cases of illness in the RSVpreF group divided by the total number of cases of illness. At 90 days, 99.5% 

confidence intervals (CIs) were used (determined by the alpha-spending function and adjusted with the use of the Bonferroni procedure), and at later intervals, 97.58% CIs were 

used (based on a two-sided alpha level of 0.0483 adjusted with the use of the Bonferroni procedure). 

Efficacy is from full phase 3 trial data, using trial dosing interval (24–36 weeks gestation).

Time period 

after birth

Events/Vaccine

(n/N)

Events/Placebo

(n/N)

Vaccine efficacy (1 – RR)

(95% CI)

Manufacturer calculated 

vaccine efficacy1 (99.5% or 

97.58% CI)

0–90 days 

after birth

6/3495 33/3480 81.9% (56.8, 92.4) 81.8% (40.6, 96.3)

0–120 days 

after birth

12/3495 46/3480 74.0% (51.1, 86.2) 73.9% (45.6, 88.8)

0–150 days 

after birth

16/3495 55/3480 71.0% (49.6, 83.4) 70.9% (44.5, 85.9)

0–180 days 

after birth

19/3495 62/3480 69.5% (49.1, 81.7) 69.4% (44.3, 84.1)
90

▪ Measures of effect

– Relative Risk: 0.487 (97.58% CI: 0.332, 0.706)

– Absolute Risk1: 1,725 fewer per 100,000 (988 to 2,246 fewer); NNV: 58 (45, 101)

– Absolute Risk2: 11,850 fewer per 100,000 (6,791 to 15,431 fewer); NNV: 8 (6, 15)

– Absolute Risk3: 5,643 fewer per 100,000 (3,234 to 7,348 fewer); NNV: 18 (14, 31)

▪ Concerns in certainty assessment: 

– None

▪ Evidence type: High

GRADE: Medically attended RSV-associated lower 

respiratory infection in infants (n=1 study)

1 Calculated using the observed outcomes in the placebo arm during the clinical trial follow-up (3.4%)

2 Calculated using rate from Lively 2019 JPIDS, 2004-2009 from 3 New Vaccine Surveillance Network (NVSN) sites from Nov-Apr season, included if with acute respiratory infection

(ARI), not restricted to lower respiratory tract infection (LRTI). 

3 Calculated assuming 47.5% of ARI from Lively et al paper were LRTI (Rainisch 2020 Vaccine)

NNV= Number needed to vaccinate
91

▪ Phase 3 RCT, MATISSE1

▪ A respiratory tract infection due to RSV that results in hospitalization

▪ Confirmed by endpoint adjudication committee (EAC)

Outcome 2: Hospitalization for RSV-associated lower 

respiratory tract infection in infants (n=1 study)

1 Kampmann B, Madhi SA, Munjal I, et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants. N Engl J Med. 2023 Apr 5. doi: 10.1056/NEJMoa2216480.
92

Outcome 2: Hospitalization for RSV-associated lower 

respiratory tract infection in infants (n=1 study)

RR= relative risk, CI= confidence interval

1 Vaccine efficacy was calculated as 1–(P/[1–P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. The confidence interval was adjusted 

using the Bonferroni procedure and accounting for the primary endpoints results. As a secondary endpoint, the criterion for vaccine efficacy was a

lower bound of the confidence interval >0%. 

2 This outcome did not meet success criterion using manufacturer calculated VE (lower bound of CI was <0%) 

Efficacy is from full phase 3 trial data, using trial dosing interval (24–36 weeks gestation).

Time period after 

birth

Events/Vaccine

(n/N)

Events/Placebo

(n/N)

Vaccine efficacy 

(1 – RR) (95% CI)

Manufacturer calculated 

vaccine efficacy1

(99.17% CI)

0–90 days after birth 10/3495 31/3480 67.9% (34.6, 84.2) 67.7% (15.9, 89.5)

0–120 days after birth 15/3495 37/3480 59.6% (26.6, 77.8) 59.5% (8.3, 83.7)

0–150 days after birth 17/3495 39/3480 56.6% (23.4, 75.4) 56.4% (5.2, 81.5)

0–180 days after birth 19/3495 44/3480 57.0% (26.5, 74.8) 56.8% (10.1, 80.7)

0–360 days after 

birth2

38/3495 57/3480 33.6% (0.2, 55.8) 33.3% (-17.6, 62.9)
93

▪ Measures of effect

– Relative risk: 0.432 (99.17% CI: 0.193, 0.899)

– Absolute risk1: 718 fewer per 100,000 (128 to 1,020 fewer); NNV: 139 (98, 781)

– Absolute risk2: 1,051 fewer per 100,000 (187 to 1,493 fewer); NNV: 95 (67, 535)

▪ Concerns in certainty assessment: 

– Serious concern for imprecision due to the width of the confidence interval 

containing estimates for which different policy decisions might be considered

▪ Evidence type: Moderate

GRADE: Hospitalization for RSV-associated lower 

respiratory tract infection in infants (n=1 study)

1 Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow-up. 

2 Calculated using the rate of acute respiratory infection (ARI) hospitalizations for infants 0-5 months (2016-2020 NVSN, unpublished) 
94

Outcome 3: ICU admission from RSV hospitalization in 

infants (n=1 study)

RR= relative risk, CI= confidence interval

1 Vaccine efficacy was calculated as 1–(P/[1–P]), where P is the number of cases in the RSVpreF group divided by the total number of cases.

Efficacy is from full phase 3 trial data, using trial dosing interval (24–36 weeks gestation).

Time period after 

birth

Events/Vaccine

(n/N)

Events/Placebo

(n/N)

Vaccine efficacy 

(1 – RR) (95% CI)

Manufacturer calculated 

vaccine efficacy1(95% CI)

0–90 days after birth 2/3495 6/3480 66.8% (-64.3, 93.3) 66.7% (-86.4, 96.7)

0–150 days after 

birth

4/3495 6/3480 33.6% (-135, 81.3) 33.3% (-181.1, 86.2)

0–180 days after 

birth

4/3495 7/3480 43.1% (-94.2, 83.3) 42.9% (-124.8, 87.7)
95

▪ Measures of effect

– Relative risk: 0.571 (95% CI: 0.123, 2.248)

– Absolute risk1: 86 fewer per 100,000 (from 176 fewer to 251 more)

– Absolute risk2: 285 fewer per 100,000 (from 583 fewer to 830 more)

▪ Concerns in certainty assessment: 

– Very serious concern for imprecision due to the width of the confidence interval 

containing estimates for which different policy decisions might be considered and 

fragility of the estimate

▪ Evidence type: Low

Outcome 3: ICU admission from RSV hospitalization in 

infants (n=1 study)

1 Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow-up.

2 Calculated using the rate of ICU admissions in hospitalizations from Arriola 2019 JPIDS and acute respiratory infection (ARI) hospitalizations for infants 0-5 months (2016-2020 

NVSN, unpublished) 
96

Outcome 4: Mechanical ventilation1from RSV 

hospitalization in infants (n=1 study)

RR= relative risk, CI= confidence interval

Efficacy is from full phase 3 trial data, using trial dosing interval (24–36 weeks gestation)

1 Invasive or non-invasive mechanical ventilation

2 Using 0.5 offset to account for zero events in the vaccine arm

3 Vaccine efficacy was calculated as 1–(P/[1–P]), where P is the number of cases in the RSVpreF group divided by the total number of cases

Time period after 

birth

Events/Vaccine

(n/N)

Events/Placebo

(n/N)

Vaccine efficacy2

(1 – RR) (95% CI)

Manufacturer calculated 

vaccine efficacy3 (95% CI)

0–90 days after 

birth

0/3495 4/3480 88.9% (-105.4, 99.4) 100% (-51.5, 100)

0–150 days after 

birth

0/3495 4/3480 88.9% (-105.4, 99.4) 100% (-51.5, 100)

0–180 days after 

birth

0/3495 5/3480 90.0% (-63.6, 99.5) 100% (-9.1, 100)
97

▪ Measures of effect

– Relative risk: 0.001 (95% CI: 0.001, 1.091)

– Absolute risk1: 144 fewer per 100,000 (144 fewer to 13 more)

– Absolute risk2: 209 fewer per 100,000 (209 fewer to 19 more)

▪ Concerns in certainty assessment: 

– Very serious concern for imprecision due to the width of the confidence interval 

containing estimates for which different policy decisions might be considered and 

fragility of the estimate

▪ Evidence type: Low

Outcome 4: Mechanical ventilation from RSV 

hospitalization in infants (n=1 study)

1 Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow-up

2 Calculated using the rate of mechanical ventilations in hospitalizations from Arriola 2019 JPIDS and acute respiratory infection (ARI) hospitalizations for infants 0-5 months (2016-

2020 NVSN, unpublished) 
98

▪ Phase 3 RCT, MATISSE and Phase 2b RCT (unpublished, data obtained from 

manufacturer)

▪ Phase 2b RCT1,2

– Pregnant people ages 18–49 in Argentina, Chile, South Africa and United States

• Infant safety set: 114 in vaccine arm (phase 3 formulation); 116 in placebo arm

▪ 1 RSV-associated death occurred in an infant in the placebo group recorded at day 120 

after birth in the Phase 3 study, no RSV-associated deaths occurred in the RSVpreF 

group

▪ No RSV-associated deaths were recorded in the Phase 2b study among those who 

received the phase 3 formulation or placebo

▪ Outcome not included in GRADE

Outcome 5: RSV-associated death in infants (n=2 studies)

1 Simões EAF, Center KJ, Tita ATN, et al. Prefusion F Protein–Based Respiratory Syncytial Virus Immunization in Pregnancy. N Engl J Med. 2022 Apr 28. doi: 

10.1056/NEJMoa2106062.

2 https://www.clinicaltrials.gov/ct2/show/study/NCT04032093
99

▪ Phase 3 RCT, MATISSE1

▪ Infant with any medically attended-RTI visit (inpatient or outpatient) AND

– Fast breathing (respiratory rate ≥60 bpm for <2 months of age [<60 days of 

age] or ≥50 bpm for ≥2 to <12 months of age) OR

– SpO2 <95% OR

– Chest wall indrawing

Outcome 6: All-cause medically attended lower respiratory 

tract infection in infants (n=1 study)
100

Outcome 6: All-cause medically attended lower respiratory 

tract infection in infants (n=1 study)

RR= relative risk, CI= confidence interval

1 Vaccine efficacy was calculated as 1–(P/[1–P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. The confidence interval was adjusted 

using the Bonferroni procedure and accounting for the primary endpoints results. As a secondary endpoint, the criterion for vaccine efficacy was a

lower bound of the confidence interval >0%. Efficacy is from full phase 3 trial data, using trial dosing interval (24–36 weeks gestation).

2 This outcome did not meet success criterion (lower bound of CI was <0%) 

Time period 

after birth

Events/Vaccine

(n/N)

Events/Placebo

(n/N)

Vaccine efficacy 

(1 – RR) (95% CI)

Manufacturer calculated 

vaccine efficacy1 (99.17% CI)

0–90 days after 

birth2

186/3495 200/3480 7.4% (-12.4, 23.7) 7.0% (-22.3, 29.3)

0–120 days after 

birth2

261/3495 278/3480 6.5% (-10, 20.5) 6.1% (-18.3, 25.5)

0–150 days after 

birth2

331/3495 349/3480 5.6% (-8.9, 18.1) 5.2% (-16.5, 22.8)

0–180 days 

after birth2

392/3495 402/3480 2.9% (-10.7, 14.8) 2.5% (-17.9, 19.4)

0–360 days 

after birth2

504/3495 531/3480 5.5% (-5.8, 15.5) 5.1% (-12.1, 19.6)
101

▪ Measures of effect

– Relative risk: 0.975 (99.17% CI: 0.806, 1.179)

– Absolute risk*: 289 fewer per 100,000 (2,241 fewer to 2,068 more)

▪ Concerns in certainty assessment

– Serious concern for imprecision due to the width of the confidence interval 

containing estimates for which different policy decisions might be considered

▪ Evidence type: Moderate

GRADE: All-cause medically attended lower respiratory 

tract infection in infants (n=1 study)

*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow-up. Absolute risk estimates should be interpreted in this 

context.
102

Outcome 7: All-cause hospitalization for lower respiratory 

tract infection in infants (n=1 study)

RR= relative risk, CI= confidence interval

1 Vaccine efficacy was calculated as 1–(P/[1–P]), where P is the number of cases in the RSVpreF group divided by the total number of cases.

Efficacy is from full phase 3 trial data, using trial dosing interval (24–36 weeks gestation).

Time period 

after birth

Events/Vaccine

(n/N)

Events/Placebo

(n/N)

Vaccine efficacy 

(1 – RR) (95% CI)

Manufacturer calculated 

vaccine efficacy1(95% CI)

0–90 days 

after birth

35/3495 55/3480 36.6% (3.4, 58.4) 36.4% (1.0, 59.6)

0–150 days 

after birth

47/3495 67/3480 30.2% (-1.10, 51.8) 29.9% (-3.4, 52.7)

0–180 days 

after birth

54/3495 76/3480 29.3% (0, 49.9) 28.9% (-2.0, 50.8)
103

▪ Measures of effect

– Relative risk: 0.711 (95% CI: 0.492, 1.020)

– Absolute risk*: 631 fewer per 100,000 (from 1,109 fewer to 44 more)

▪ Concerns in certainty assessment

– Serious concern for imprecision due to the width of the confidence interval 

containing estimates for which different policy decisions might be considered

▪ Evidence type: Moderate

Outcome 7: All-cause hospitalization for lower respiratory 

tract infection in infants (n=1 study)

*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow-up. Absolute risk estimates should be interpreted in this 

context.
104

Harms
105

▪ Phase 3 RCT, MATISSE (unpublished, data obtained directly from 

manufacturer)

– Maternal safety set: 3,682 participants in vaccine arm; 3,675 in placebo arm

▪ Phase 2b RCT (unpublished, data obtained directly from manufacturer)

– Maternal safety set: 115 participants in vaccine arm (phase 3 formulation); 

117 in placebo arm

▪ Follow up times for serious adverse events reported by maternal 

participants were from vaccination through 6 months after delivery 

(Phase 3) or throughout the study (Phase 2b)

Outcome 8: Serious adverse events in pregnant people (n=2 

studies)
106

Outcome 8: Serious adverse events in pregnant people (n=2 

studies)

CI= confidence interval

Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document- FDA

Trial Events/Vaccine

(n/N)

Events/Placebo

(n/N)

Relative Risk (95% CI)

Phase 3 598/3682 (16.2%) 558/3675 (15.1%) 1.07 (0.96, 1.19)

Phase 2b 7/115 (6.1%) 14/117 (12.0%) 0.51 (0.21, 1.21)

Serious adverse events in four vaccine recipients (pain in an arm followed by bilateral lower extremity pain, 

premature labor, systemic lupus erythematosus, and eclampsia) and in one placebo recipient (premature placental 

separation) were assessed by the investigator as being related to the injection. Based on review of the event 

narratives and temporal association of these events to vaccination, FDA agreed with the investigator’s 

assessments that there was a reasonable possibility that these events were related to the study intervention.
107

▪ Measures of effect

– Relative risk: 1.06 (95% CI: 0.95, 1.17)

– Absolute risk*: 905 more per 100,000 (754 fewer to 2,564 more)

▪ Concerns in certainty assessment

– Serious concern for imprecision due to the width of the confidence interval 

containing estimates for which different policy decisions might be considered

– Serious concern for indirectness as 55% of the Phase 3 RCT and 62% of the Phase 2b 

RCT did not receive vaccine or placebo in the approved dosing interval (32–36 weeks 

gestation). In the approved dosing interval, there is less opportunity for serious 

adverse events, including preterm birth/delivery, compared to the trial dosing 

interval (24–36 weeks gestation).

▪ Evidence type: Low

GRADE: Serious adverse events in pregnant people (n=2 

studies)

*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow-up. Absolute risk estimates should be interpreted in this 

context. CI= confidence interval
108

▪ Phase 3 RCT, MATISSE and Phase 2b (unpublished, data obtained directly 

from manufacturer)

▪ Participants reported local and systemic reactions up to 7 days after 

vaccination

Outcome 9: Reactogenicity (grade 3+) in pregnant people 

(n=2 studies)
109

Outcome 9: Reactogenicity (grade 3+) in pregnant people 

Trial Outcome Events/Vaccine

(n/N)

Events/Placebo

(n/N)

Relative Risk (95% CI)

Phase 3 Local events (grade 3+) 11/3663 (0.3%) 0/3639 (0%) 21.86 (1.29, 371.74)

Systemic events (grade 3+) 83/3663 (2.3%) 83/3640 (2.3%) 0.99 (0.74, 1.34)

Phase 2b Local events (grade 3+) 0/114 (0%) 0/117 (0%) 1.03 (0.02, 51.28)*

Systemic events (grade 3+) 2/114 (1.8%) 4/117 (3.4%) 0.51 (0.10, 2.75)

Grade 3: prevents daily routine activity. For redness or swelling is >10 cm. For vomiting, requires intravenous hydration. For 

diarrhea, includes 6 or more loose stools in 24 hours. Grade 4: requires emergency room visit or hospitalization; for redness

included necrosis or exfoliative dermatitis; for swelling included necrosis. 

*Using 0.5 offset to account for zero events

CI= confidence interval
110

▪ Measures of effect

– Relative risk: 0.97 (95% CI: 0.72, 1.31)

– Absolute risk*: 69 fewer per 100,000 (648 fewer to 718 more)

▪ Concerns in certainty assessment: 

– Serious concern for indirectness as this data only includes systemic 

reactions. When selecting the a priori harm outcomes, the Work Group 

defined reactogenicity as both local and systemic reactions.

▪ Evidence type: Moderate

Outcome 9: Reactogenicity (grade 3+) in pregnant people 

(n=2 studies)

*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow-up. Absolute risk estimates should be interpreted in this 

context. CI= confidence interval
111

▪ Phase 3 RCT, MATISSE (unpublished, data obtained directly from 

manufacturer)

– Infant safety set: 3,568 in vaccine arm; 3,558 in placebo arm

▪ Phase 2b RCT (unpublished, data obtained directly from manufacturer)

– Infant safety set: 114 in vaccine arm (phase 3 formulation); 116 in placebo 

arm

Outcome 10: Serious adverse events in infants (n=2 studies)
112

Outcome 10: Serious adverse events in infants (n=2 studies)

Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document- FDA, CI= confidence interval

Trial Events/Vaccine

(n/N)

Events/Placebo

(n/N)

Relative Risk (95% CI)

Phase 3 625/3568 (17.5%) 623/3558 (17.5%) 1.00 (0.90, 1.11)

Phase 2b 41/114 (36.0%) 38/116 (32.8%) 1.10 (0.77, 1.57)

No serious adverse events in infants were considered by the investigators to be related to the vaccine. For infant deaths in the

RSVpreF group, the FDA agreed with the investigator’s conclusions for 4 out of 5 of the infant deaths; however, for 1 case of

extreme prematurity in an infant born to an 18-year-old mother at 10 days after vaccination who died from prematurity-related 

complications, FDA was unable to exclude the possibility of the extreme prematurity and subsequent death being related to 

receipt of the investigational product. No non-fatal SAEs in infant participants were considered related to maternal vaccination by 

FDA.
113

▪ Measures of effect

– Relative risk: 1.01 (95% CI: 0.91, 1.11)

– Absolute risk*: 180 more per 100,000 (1,619 fewer to 1,979 more)

▪ Concerns in certainty assessment

– Serious concern for imprecision due to the width of the confidence interval 

containing estimates for which different policy decisions might be considered

– Serious concern for indirectness as 55% of the Phase 3 RCT and 62% of the Phase 2b 

RCT did not receive vaccine or placebo in the approved dosing interval (32–36 weeks 

gestation). In the approved dosing interval, there is less opportunity for serious 

adverse events, including preterm birth/delivery, compared to the trial dosing 

interval (24–36 weeks gestation)

▪ Evidence type: Low

GRADE: Serious adverse events in infants (n=2 studies)

CI= confidence interval
114

▪ Phase 3 RCT, MATISSE and Phase 2b (unpublished, data obtained directly 

from manufacturer)

–Gestational age at birth <37 weeks and <34 weeks

Outcome 11: Preterm births (n=2 studies)
115

Outcome: Preterm births (n=2 studies), Pfizer maternal 

RSVpreF vaccine

*When reported as an adverse event of special interest, 202 preterm births occurred in the vaccine arm; the relative risk is minimally changed at 1.19 (0.98, 1.45) when using this 

count

**Using 0.5 offset to account for zero events in the vaccine arm

CI= confidence interval

Publication Definition Events/Vaccine

(n/N)

Events/Placebo

(n/N)

Relative Risk (95% CI)

Phase 3

<34 weeks 21/3568 12/3558 1.75 (0.86, 3.54)

<37 weeks 201*/3568 169/3558 1.19 (0.97, 1.45)

Phase 2b

<34 weeks 0/115 1/117 0.34 (0.01, 8.24)**

<37 weeks 6/115 3/117 2.03 (0.52, 7.94)
116

▪ Measures of effect

– Relative risk: 1.20 (0.99, 1.46)

– Absolute risk*: 936 more per 100,000 (from 47 fewer to 2,153 more)

▪Concerns in certainty assessment:

– Very serious concern for imprecision due to the width of the confidence interval 

containing estimates for which different policy decisions might be considered and 

not meeting optimal information size requirements

– Serious concern for indirectness as 55% of the Phase 3 RCT and 62% of the Phase 2b 

RCT did not receive vaccine or placebo in the approved dosing interval (32–36 weeks 

gestation). In the approved dosing interval, there is less opportunity for serious 

adverse events, including preterm birth/delivery, compared to the trial dosing 

interval (24–36 weeks gestation)

▪ Evidence type: Very low

Outcome: Preterm births (n=2 studies)

*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow-up. Absolute risk estimates should be interpreted in this 

context. CI= confidence interval
117

GRADE additional slides
118

Inclusion/exclusion criteria for pregnant people-Phase 3 Trial

Inclusion Exclusion

Healthy women ≤49 years of age who are 

between 24 0/7 and 36 0/7 weeks of gestation on 

the day of planned vaccination, with an 

uncomplicated, singleton pregnancy, who are at 

no known increased risk for complications.

Willing and able to comply with scheduled 

visits, treatment plan, laboratory tests, and 

other study procedures.

Receiving prenatal standard of care based on 

country requirements.

Had a fetal anomaly ultrasound examination 

performed at ≥18 weeks of pregnancy with no 

significant fetal abnormalities observed.

Determined by medical history, physical 

examination, and clinical judgment to be 

appropriate for inclusion in the study.

Documented negative HIV antibody test, 

syphilis test, and hepatitis B virus (HBV) surface 

antigen test during this pregnancy and prior to 

randomization (Visit 1).

Intention to deliver at a hospital or birthing 

facility where study procedures can be 

obtained.

Expected to be available for the duration of the 

study and can be contacted by telephone during 

study participation.

Participant is willing to give informed consent 

for her infant to participate in the study.

Capable of giving signed informed consent 

which includes compliance with the 

requirements and restrictions listed in the 

informed consent document (ICD) and in this 

protocol OR If the maternal participant is 

illiterate, a thumbprinted informed consent 

must be obtained, which must be signed and 

dated by an impartial witness who was present 

throughout the entire informed consent process 

confirming that the maternal participant has 

been informed of all pertinent aspects of the 

study.

Prepregnancy body mass index (BMI) of >40 kg/m2. If prepregnancy BMI is not available, the BMI at the time of the first obstetric visit during the current pregnancy may be used.

Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.

History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any component of the investigational product or any related vaccine.

Current pregnancy resulting from in vitro fertilization.

Current pregnancy complications or abnormalities at the time of consent that will increase the risk associated with the participation in and completion of the study, including but not 

limited to the following:

Preeclampsia, eclampsia, or uncontrolled gestational hypertension.

Placental abnormality.

Polyhydramnios or oligohydramnios.

Significant bleeding or blood clotting disorder.

Endocrine disorders, including untreated hyperthyroidism or untreated hypothyroidism. This also includes disorders of glucose intolerance (e.g., diabetes mellitus type 1 or 2) antedating 

pregnancy or occurring during pregnancy if uncontrolled at the time of consent.

Any signs of premature labor with the current pregnancy or having ongoing intervention (medical/surgical) in the current pregnancy to prevent preterm birth.

Prior pregnancy complications or abnormalities at the time of consent, based on the investigator's judgment, that will increase the risk associated with the participation in and completion 

of the study, including but not limited to the following:

Prior preterm delivery ≤34 weeks' gestation.

Prior stillbirth or neonatal death.

Previous infant with a known genetic disorder or significant congenital anomaly.

Major illness of the maternal participant or conditions of the fetus that, in the investigator's judgment, will substantially increase the risk associated with the maternal or infant participant's 

participation in, and completion of, the study or could preclude the evaluation of the maternal participant's response (includes positive serologic testing for regional endemic conditions 

assessed during routine maternal care, as per local standards of care and obstetric recommendations).

Congenital or acquired immunodeficiency disorder, or rheumatologic disorder or other illness requiring chronic treatment with known immunosuppressant medications, including 

monoclonal antibodies, within the year prior to enrollment.

Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk 

associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make 

the participant inappropriate for entry into this study.

Participation in other studies involving investigational drug(s) within 28 days prior to consent and/or during study participation.

Receipt of monoclonal antibodies within the year prior to enrollment or the use of systemic corticosteroids for >14 days within 28 days prior to study enrollment. Permitted treatments 

include the receipt of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies, prednisone doses of <20 mg/day for ≤14 days and, inhaled/nebulized, intraarticular, intrabursal, or topical (skin or eyes) corticosteroids.

Current alcohol abuse or illicit drug use. Note: Marijuana use is not considered an exclusion criterion for the study when elicited in participant screening, though it may be considered illicit 

in some locales.

Receipt of blood or plasma products or immunoglobulin (Ig), from 60 days before investigational product administration, or planned receipt through delivery, with 1 exception, Rho(D) 

immune globulin (e.g., RhoGAM), which can be given at any time.

Previous vaccination with any licensed or investigational RSV vaccine or planned. Note: Licensed COVID-19 vaccines or COVID-19 vaccines authorized for temporary or emergency use will 

not be prohibited during the course of this study.

Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Pfizer employees, 

including their family members, directly involved in the conduct of the study.

Participants who are breastfeeding at the time of enrollment.
119

Inclusion/exclusion criteria for infants-Phase 3 Trial

Inclusion Exclusion

Evidence of a signed and dated informed consent document signed by 

the parent(s)/legal guardian(s) OR If the infant participant's maternal 

participant/parent(s)/legal guardian(s) is illiterate, a thumbprinted

informed consent must have been obtained, which must have been 

signed and dated by an impartial witness who was present throughout the 

entire informed consent process confirming that the maternal 

participant/parent(s)/legal guardian(s) has been informed of all pertinent 

aspects of the study for herself (maternal participant) and her fetus/infant 

prior to taking part in the study.

Parent(s)/legal guardian(s) willing and able to comply with scheduled 

visits, treatment plan, laboratory tests, and other study procedures.

Infant who is a direct descendant (e.g., child or 

grandchild) of the study personnel.
120

Inclusion/exclusion criteria for pregnant people-Phase 2b

Inclusion-Pregnant people Exclusion-Pregnant people

Healthy women 18 to 49 years of age between 24 

and 36 weeks of gestation on the day of planned 

vaccination, with an uncomplicated pregnancy, who 

are at no known increased risk for complications, and 

whose fetus has no significant abnormalities 

observed on ultrasound.

Willing and able to comply with scheduled visits, 

treatment plan, laboratory tests, and other study 

procedures.

Receiving prenatal standard of care.

Had an ultrasound performed at >=18 weeks of 

pregnancy.

Had a negative urinalysis for protein and glucose at 

the screening visit. Trace protein in the urine is 

acceptable if the blood pressure is also normal.

Determined by medical history, physical 

examination, screening laboratory assessment, and 

clinical judgment to be appropriate for inclusion in 

the study.

Documented negative human immunodeficiency 

virus antibody, hepatitis B virus surface antigen, 

hepatitis C virus antibody, and syphilis tests at the 

screening visit.

Body mass index of </=40 kg/m2 at the time of the 

screening visit.

Capable of giving signed informed consent, which 

includes compliance with the requirements and 

restrictions listed in the informed consent document 

and in this protocol.

Expected to be available for the duration of the 

study and willing to give informed consent for her 

infant to participate in the study.

Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate 

intramuscular injection.

History of severe adverse reaction associated with a vaccine and/or severe allergic reaction to any component of the investigational product 

or any related vaccine.

History of latex allergy.

History of any severe allergic reaction.

Participants with known or suspected immunodeficiency.

Current pregnancy resulting from in vitro fertilization or other assisted reproductive technology.

A prior history of or known current pregnancy complications or abnormalities that will increase the risk associated with the participant's 

participation in and completion of the study.

Major illness of the mother or conditions of the fetus that, in the investigator's judgment, will substantially increase the risk associated with 

the participant's participation in, and completion of, the study or could preclude the evaluation of the participant's response.

Participant with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention including but not 

limited to systemic or cutaneous lupus erythematosus, autoimmune arthritis/rheumatoid arthritis, Guillain-Barré syndrome, multiple 

sclerosis, Sjögren's syndrome, idiopathic thrombocytopenia purpura, glomerulonephritis, autoimmune thyroiditis, giant cell arteritis 

(temporal arteritis), psoriasis, and insulin-dependent diabetes mellitus (type 1).

Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or 

laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may 

interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for 

entry into this study.

Participation in other studies involving investigational drug(s) within 28 days prior to study entry and/or during study participation.

Participants who receive treatment with immunosuppressive therapy including cytotoxic agents or systemic corticosteroids (such as for 

cancer or an autoimmune disease), or planned receipt of such treatment or agents during study participation. If systemic corticosteroids 

have been administered short term (<14 days) for treatment of an acute illness, participants should not be enrolled into the study until 

corticosteroid therapy has been discontinued for at least 30 days before investigational product administration. Inhaled/nebulized, intra 

articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.

Current alcohol abuse or illicit drug use.

Receipt of blood or plasma products or immunoglobulin, from 60 days before investigational product administration, or planned receipt 

through delivery, with 1 exception, Rho(D) immune globulin (eg, RhoGAM), which can be given at any time.

Previous vaccination with any licensed or investigational RSV vaccine or planned receipt during study participation.

Laboratory test results at the screening visit outside the normal reference value for pregnant women according to their trimester in 

pregnancy.

Participants who are breastfeeding at the time of the screening visit.
121

Inclusion/exclusion criteria for infants-Phase 2b

Inclusion-Infants Exclusion-Infants

Evidence of a signed and dated informed consent document 

signed by the parent(s).

Parent(s) willing and able to comply with scheduled visits, 

treatment plan, laboratory tests, and other study procedures.

Infant who is a direct descendant (eg, child or grandchild) of the 

study personnel.
122

Figure 1. Enrollment, 

Randomization, 

Administration of Vaccine or 

Placebo, and Follow-up

Kampmann B, Madhi SA, Munjal I, et al. 

Bivalent Prefusion F Vaccine in 

Pregnancy to Prevent RSV Illness in 

Infants. N EnglJ Med. 2023 Apr 5. doi: 

10.1056/NEJMoa2216480.
123

Table 1. Demographics of phase 3 trial

Kampmann B, Madhi SA, Munjal I, et al. 

Bivalent Prefusion F Vaccine in Pregnancy to 

Prevent RSV Illness in Infants. N Engl J Med. 

2023 Apr 5. doi: 10.1056/NEJMoa2216480.
124

Severity scale for local reactions and systemic events 

(maternal participants)

Kampmann B, Madhi SA, Munjal I, et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants. N Engl J Med. 2023 Apr 5. doi: 10.1056/NEJMoa2216480.
125

Studies Included in the Review of Evidence

Last name first 

author, Publication 

year

Study 

design

Country Age 

mean 

(SD), 

years

Total Population N intervention N comparison Outcomes Funding 

Source

Kampmann B, 

et al. plus unpublished 

data obtained directly 

from the manufacturer 

RCT Argentina, Australia, 

Brazil, Canada, Chile, 

Denmark, Finland, 

Gambia, Japan, 

Republic of Korea, 

Mexico, Netherlands, 

New Zealand, 

Philippines, South 

Africa, Spain, Taiwan, 

United States

29.0 

(5.7)

7,357 3,682 3,675 Medically attended 

RSV-associated lower 

respiratory infection in 

infants; Hospitalization 

for RSV-associated 

lower respiratory tract 

infection in infants; 

RSV-associated death 

in infants; All cause 

medically attended 

lower respiratory tract 

infection in infants; 

Serious adverse events 

in pregnant people; 

Reactogenicity in 

pregnant people; 

Serious adverse events 

in infants; Preterm 

birth

Pfizer

Pfizer, Phase 2 Trial 

plus unpublished data 

obtained directly from 

the manufacturer 

RCT Argentina, Chile, 

South Africa and the 

United States

27.1

(5.2)

232 115 (phase 3 

formulation)

117 RSV-associated death 

in infants; Serious 

adverse events in 

pregnant people; 

Reactogenicity in 

pregnant people;

Serious adverse events 

in infants; Preterm 

birth;

Pfizer
126

Summary of Studies Reporting Outcome 1: Medically 

attended RSV-associated lower respiratory infection in 

infants 

Absolute difference was calculated using the observed outcomes in the placebo arm during the available clinical trial follow-up.Absolute difference estimates should be 

interpreted in this context.

Last name 

first author, 

Publication 

year

Age 

mean 

(SD), 

years

N 

intervention

N 

comparison

Comparator 

Vaccine

Absolute 

difference/effect 

estimate 

(97.58% CI)

Study 

limitations 

(Risk of Bias)

Kampmann B, 

et al.

29.0

(5.7)

3495 3480 Placebo 1,725 fewer per 

100,000 (988 to 

2,246 fewer)

None
127

Summary of Studies Reporting Outcome 2: 

Hospitalization for RSV-associated lower respiratory 

tract infection in infants 

Absolute difference was calculated using the observed outcomes in the placebo arm during the available clinical trial follow-up.Absolute difference estimates should be 

interpreted in this context.

Last name first 

author, 

Publication 

year

Age 

mean 

(SD), 

years

N 

interventio

n

N 

comparison

Comparato

r Vaccine

Absolute 

difference/effect 

estimate 

(99.17% CI)

Study 

limitations 

(Risk of Bias)

Kampmann B, 

et al.

29.0 

(5.7)

3495 3480 Placebo 718 fewer per 

100,000 (128 to 

1,020 fewer)

None
128

Summary of Studies Reporting Outcome 3: ICU 

admission from RSV hospitalization in infants

Absolute difference was calculated using the observed outcomes in the placebo arm during the available clinical trial follow-up.Absolute difference estimates should be 

interpreted in this context.

Last name first 

author, 

Publication 

year

Age 

mean 

(SD), 

years

N 

intervention

N 

comparison

Comparator 

Vaccine

Absolute 

difference/effect 

estimate (95% CI)

Study 

limitations 

(Risk of Bias)

Data received 

directly from 

the 

manufacturer

29.0 

(5.7)

3495 3480 Placebo 86 fewer per 

100,000 (176 

fewer to 251 

more)

None
129

Summary of Studies Reporting Outcome 4: Mechanical 

ventilation from RSV hospitalization in infants

Absolute difference was calculated using the observed outcomes in the placebo arm during the available clinical trial follow-up.Absolute difference estimates should be 

interpreted in this context.

Last name first 

author, 

Publication 

year

Age 

mean 

(SD), 

years

N 

interventio

n

N 

comparison

Comparato

r Vaccine

Absolute 

difference/effect 

estimate (95% 

CI)

Study 

limitations 

(Risk of Bias)

Data received 

directly from 

the 

manufacturer

29.0 

(5.7)

3495 3480 Placebo 144 fewer per 

100,000 (144 

fewer to 13 more)

None
130

Summary of Studies Reporting Outcome 5: RSV-associated 

death in infants 

Last name first 

author, 

Publication 

year

Age 

mean 

(SD), 

years

N 

intervention

N 

compariso

n

Comparator 

Vaccine

Absolute 

difference/eff

ect estimate

Study 

limitations 

(Risk of Bias)

Kampmann B, 

et al.

29.0

(5.7)

3495 3480 Placebo Not estimable 

1 death in a 

placebo 

recipient

None

Phase 2b RCT, 

unpublished

18-49 

(range)

114 116 Placebo Not estimable 

0 deaths in trial

None
131

Summary of Studies Reporting Outcome 6: All-cause 

medically attended lower respiratory tract infection in 

infants 

Absolute difference was calculated using the observed outcomes in the placebo arm during the available clinical trial follow-up.Absolute difference estimates should be 

interpreted in this context.

Last name first 

author, 

Publication 

year

Age 

mean 

(SD), 

years

N 

interventio

n

N 

comparison

Comparator 

Vaccine

Absolute 

difference/effect 

estimate 

(99.17% CI)

Study 

limitations 

(Risk of Bias)

Kampmann B, 

et al.

29.0 

(5.7)

3495 3480 Placebo 289 fewer per 

100,000 (2,241 

fewer to 2,068 

more)

None
132

Summary of Studies Reporting Outcome 7: All-cause 

hospitalization for lower respiratory tract infection in 

infants

Absolute difference was calculated using the observed outcomes in the placebo arm during the available clinical trial follow-up.Absolute difference estimates should be 

interpreted in this context.

Last name first 

author, 

Publication 

year

Age 

mean 

(SD), 

years

N 

interventio

n

N 

comparison

Comparator 

Vaccine

Absolute 

difference/effect 

estimate (95% 

CI)

Study 

limitations 

(Risk of Bias)

Data received 

directly from 

the 

manufacturer

29.0 

(5.7)

3495 3480 Placebo 631 fewer per 

100,000 (1,109 

fewer to 44 

more)

None
133

Summary of Studies Reporting Outcome 8: Serious adverse 

events in pregnant people 

Last name first 

author, 

Publication 

year

Age 

mean 

(SD), 

years

N 

intervention

N 

compariso

n

Comparato

r Vaccine

Relative 

difference/effect 

estimate

Study 

limitations 

(Risk of Bias)

Kampmann B, 

et al.

29.0 

(5.7)

3682 3675 Placebo RR: 1.07 (0.96, 

1.19)

None

Phase 2b RCT 27.1

(5.2)

115 117 Placebo RR: 0.51 (0.21, 

1.21)

None
134

Summary of Studies Reporting Outcome 9: Reactogenicity 

(grade 3+) in pregnant people 

Last name 

first author, 

Publication 

year

Age 

mean 

(SD), 

years

N 

interventio

n

N 

comparison

Comparato

r Vaccine

Relative 

difference/effect 

estimate

Study 

limitations 

(Risk of Bias)

Kampmann B, 

et al.

29.0 

(5.7)

3663 3640 Placebo RR: 0.99 (0.74, 

1.34)

None

Phase 2b RCT 27.1

(5.2)

114 117 Placebo RR: 0.51 (0.10, 

2.75)

None
135

Summary of Studies Reporting Outcome 10: Serious 

adverse events in infants 

Last name first 

author, 

Publication year

Age median 

(range)

N intervention N comparison Comparator 

Vaccine

Relative 

difference/effect 

estimate

Study 

limitations 

(Risk of Bias)

Kampmann B, 

et al. 

11.97 

months 

(0.0, 24.3) 

3568 3558 Placebo RR: 1.00 (0.90, 

1.11)

None

Phase 2b RCT 114 116 Placebo RR: 1.10 (0.77, 

1.57)

None
136

Summary of Studies Reporting Outcome 11: Preterm birth

Last name first 

author, 

Publication year

Age mean 

(SD)

N intervention N comparison Comparator 

Vaccine

Relative 

difference/effect 

estimate

Study 

limitations 

(Risk of Bias)

Kampmann B, 

et al.

11.97 

months 

(0.0, 24.3)

3568 3558 Placebo RR: 1.19 (0.97, 

1.45)

None

Phase 2b RCT 115 117 Placebo RR: 2.03 (0.52, 

7.94)

None
137

Grade Summary of Findings Table- Benefits

No of 

studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Intervention Comparison Relative(CI)

Absolute

(CI) Importance Certainty

Medically attended RSV-associated lower respiratory infection in infants

1 Randomized 

studies

Not 

serious

Not serious Not serious Not serious None 57/3495 (1.6%) 117/3480 

(3.4%)

0.487 

(97.58% CI: 

0.332, 0.706)

1,725 fewer per 

100,000 (988 to 

2,246 fewer)

Critical High

23.1% 11,850 fewer per 

100,000 (6,791 to 

15,431 fewer)

11.0% 5,643 fewer per 

100,000 (3,234 to 

7,348 fewer)

Hospitalizations RSV-associated lower respiratory infection in infants

1 Randomized 

studies

Not 

serious

Not serious Not serious Serious None 19/3495 (0.5%) 44/3480 (1.3%) 0.432 

(99.17% CI: 

0.193, 

0.899)

718 fewer per 

100,000 (128 to 

1,020 fewer)

Critical Low

1.9% 1,051 fewer per 

100,000 (187 to 

1,493 fewer)

ICU admission from RSV hospitalization

1 Randomized 

studies

Not 

serious

Not serious Not serious Very serious None 4/3495 (0.1%) 7/3480 (0.2%) 0.571 (95% 

CI: 0.123, 

2.248)

86 fewer per 

100,000 (176 fewer 

to 251 more)

Important Low

0.7% 285 fewer per 

100,000 (583 fewer 

to 830 more)
138

Grade Summary of Findings Table- Benefits

No of 

studies

Study 

design

Risk of 

bias Inconsistency Indirectness Imprecision Other considerations Intervention Comparison Relative(CI)

Absolute

(95% CI) Importance Certainty

Mechanical ventilation from RSV hospitalization

1 Randomized 

studies

Not 

serious

Not serious Not serious Very serious None 0/3495 (0.0%) 5/3480 (0.1%) 0.001 

(95% CI: 

0.001, 

1.091)

144 fewer 

per 100,000 

(144 fewer 

to 13 more)

Important Low

0.2% 209 fewer 

per 100,000 

(209 fewer 

to 19 more)

All-cause medically attended lower respiratory tract infection in infants

1 Randomized 

studies

Not 

serious

Not serious Not serious Serious None 392/3495 

(11.2%)

402/3480 

(11.6%)

0.975 

(99.17% CI: 

0.806, 

1.179)

289 fewer 

per 100,000 

(2,241 fewer 

to 2,068 

more)

Important Moderate

All-cause hospitalization for lower respiratory tract infection in infants

1 Randomized 

studies

Not 

serious

Not serious Not serious Serious None 54/3495 (1.5%) 76/3480 (2.2%) 0.711 (95% 

CI: 0.492, 

1.010)

631 fewer 

per 100,000 

(1,109 fewer 

to 44 more)

Important Moderate
139

Grade Summary of Findings Table- Harms

No of 

studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Intervention comparison Relative(95% CI)

Absolute

(95% CI) Importance Certainty

Serious adverse events in pregnant women

2 Randomized 

studies

Not 

serious

Not serious Serious Serious None 605/3797 

(15.9%)

572/3792 

(15.1%)

1.06 

(0.95, 

1.17)

905 more 

per 100,000 

(754 

fewer to 

2,564 more)

Critical Low

Reactogenicity (3+ or higher) in pregnant women

2 Randomized 

studies

Not 

serious

Not serious Serious Not serious None 85/3777 

(2.3%)

87/3757 (2.3%) 0.97 

(0.72, 

1.31)

69 fewer per 

100,000 

(648 fewer 

to 718 more)

Important Moderate

Serious adverse events in infants

2 Randomized 

studies

Not 

serious

Not serious Serious Serious None 666/3682 

(18.1%)

661/3674 

(18.0%)

1.01 

(0.91, 

1.11)

180 more 

per 100,000 

(1,619 fewer 

to 1,979 

more)

Critical Low

Preterm birth

2 Randomized 

studies

Not 

serious

Not serious Serious Very serious None 207/3683 

(5.6%)

172/3675 

(4.7%)

1.20 

(0.99, 

1.46)

936 more 

per 100,000 

(47 fewer to 

2,153 more)

Critical Very low