Centers for Disease Control and Prevention

Evidence to Recommendations Framework: 

Pfizer Maternal RSVpreF Vaccine

Katherine 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

June 22, 2023
2

Evidence to Recommendations (EtR) Framework

Policy Question

▪ Should vaccination with Pfizer RSVPreF vaccine (120μg antigen, 1 dose 

IM given 24–36 weeks gestation) be recommended for pregnant people 

to prevent RSV disease in infants?

RSVpreF is a bivalent recombinant stabilized prefusion F protein subunit vaccine
3

Evidence to Recommendations (EtR) Framework

PICO Question

▪Population Pregnant people 24–36 weeks gestation

Intervention Pfizer RSVPreF Vaccine

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
4

Evidence to Recommendations (EtR) Framework

EtR Domain Question(s)

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

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

▪ How substantial are the undesirable anticipated effects?

▪ Do the desirable effects outweigh the undesirable effects?

Values ▪ Does the target population feel the desirable effects are large relative 

to the undesirable effects?

▪ Is there important variability in how patients value the outcome?

Acceptability ▪ Is the intervention acceptable to key stakeholders?

Feasibility ▪ Is the intervention feasible to implement?

Resource Use ▪ Is the intervention a reasonable and efficient allocation of resources?

Equity ▪ What would be in the impact of the intervention on health equity?
EtR Domain: Public Health Problem

Is the problem of public health importance?
6

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

infants1

▪ 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

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
7

Seasonality of RSV transmission — National Respiratory 

and Enteric Virus Surveillance System, NREVSS1, 2017–

2020

0

5

10

15

20

25

27 29 31 33 35 37 39 41 43 45 47 49 51 1 3 5 7 9 11 13 15 17 19 21 23 25

Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun

% PCR results RSV

-positive

Epidemiologic week

Abbreviation: PCR = polymerase chain reaction; RSV = respiratory syncytial virus. 1. https://www.cdc.gov/mmwr/volumes/72/wr/mm7214a1.htm

* 3-week centered moving averages of percentage of RSV-positive PCR results nationwide. The black dotted line represents the threshold for a seasonal epidemic (3% RSV-positive laboratory PCR results). 
8

Changes in seasonality of RSV transmission following 

SARS-CoV2 introduction— NREVSS1, 2017–2023

0

5

10

15

20

25

27 29 31 33 35 37 39 41 43 45 47 49 51 1 3 5 7 9 11 13 15 17 19 21 23 25

Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun

% PCR results RSV

-positive

Epidemiologic week

2017–18 2018–19 2019–20 2020–21 2021–22 2022–23

Abbreviation: PCR = polymerase chain reaction; RSV = respiratory syncytial virus. 1. https://www.cdc.gov/mmwr/volumes/72/wr/mm7214a1.htm

* 3-week centered moving averages of percentage of RSV-positive PCR results nationwide. The black dotted line represents the threshold for a seasonal epidemic (3% RSV-positive laboratory PCR results). 
9

Public Health Problem- Work Group Interpretation

▪ Is RSV among infants of public health importance? 

No Probably 

No

Probably 

Yes Yes Varies Don’t know
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?
11

GRADE Outcomes, Importance, and Data Sources: 

Pfizer maternal RSVpreF vaccine

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 No data

Mechanical ventilation from RSV hospitalization in infants Important No data

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 No data

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) Critical Phase 3 and phase 2b2 RCT

RCT = Randomized-controlled trial

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 were included
12

Efficacy estimates and concerns in certainty of 

assessment, benefits: Pfizer maternal RSVpreF vaccine

Outcome Importance1 Data sources Manufacturer 

calculated vaccine 

efficacy (97.58% or 

99.17% CI) 2

Concerns in certainty 

assessment

Benefits

Medically attended RSV-associated lower respiratory tract infection in 

infants (0–180 days)

Critical Phase 3 RCT 51.3% (29.4, 66.8) None

Hospitalization for RSV-associated lower respiratory tract infection in 

infants (0–180 days)

Critical Phase 3 RCT 56.8% (10.1, 80.7) Imprecision (serious)3

ICU admission from RSV hospitalization in infants Important No data

Mechanical ventilation from RSV hospitalization in infants Important No data

RSV-associated death in infants Important Phase 3 and phase 2b4

RCT

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

phase 3 trial that was recorded at day 120 after birth. No 

RSV-associated 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% (-17.9, 19.4) Imprecision (serious)3

All-cause hospitalization for lower respiratory tract infection in infants Important No data

RCT = Randomized-controlled trial

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. 97.58% confidence interval used for medically attended RSV-associated lower 

respiratory tract infection in infants, 99.17% confidence interval used for other endpoints. 

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

4 Among phase 2b trial participants, only those who received the vaccine formulation of the phase 3 trial were included
13

Efficacy estimates and concerns in certainty of 

assessment, harms: Pfizer maternal RSVpreF vaccine

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 2b2 RCT

1.06 (0.95, 1.17) Imprecision (serious)3

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

phase 2b2 RCT

0.97 (0.72, 1.31) Indirectness (serious) 4

Serious adverse events in infants Critical Phase 3 and 

phase 2b2 RCT

1.01 (0.91, 1.11) Imprecision (serious) 3

Preterm birth (<37 weeks) Critical Phase 3 and 

phase 2b2 RCT

1.20 (0.99, 1.46) Imprecision (very serious) 5

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

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

4 Serious concern for indirectness as these data only includes systemic reactions 

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 not 

meeting optimal information size requirements
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 No data Not evaluated

Mechanical ventilation from RSV hospitalization in 

infants 

Important No data Not evaluated

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 all-cause 

medically attended lower respiratory tract infection in infants 

Moderate

All-cause hospitalization for lower respiratory tract 

infection in infants 

Important No data Not evaluated

Harms

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

groups

Moderate

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 Moderate

Preterm birth (<37 weeks) Critical RCT (2) Preterm births were unbalanced between vaccine and placebo groups Low
15

Summary of GRADE: Pfizer maternal RSVpreF vaccine

15

Overall 

evidence type: 

Low
16

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

RSVpreF vaccine

16

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)

*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
17

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

RSVpreF vaccine

▪ Measures of effect

– Relative risk: 1.20 (0.99, 1.46)

– Absolute risk*: 9 more per 1,000 (from 0 fewer to 22 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

▪ Evidence type: Low

*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.
18

Preterm birth rates in maternal RSV vaccine clinical 

trials: GSK

▪ 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

▪ 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

Study vaccine given at 240/7 to 340/7 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 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)
19

Preterm birth rates in maternal RSV vaccine clinical 

trials: Novavax

▪ Phase 3 clinical trial in 4,636 women randomized 2:1, vaccine to placebo

▪ Vaccine formulation: 120μg of recombinant RSV F protein nanoparticle vaccine 

adsorbed to 0.4mg of aluminum (Novavax vaccine was not stabilized in the 

prefusion form)

▪ Maternal vaccine did not reach primary efficacy endpoints and thus did not move 

forward, but there were no safety concerns (preterm births or other) in this trial 

Preterm Birth Definition Preterm Birth in Vaccine group, 

n (%)

N=2,986

Preterm Birth in Placebo, 

n (%)

N=1,554

<37 weeks among infants* 175 (5.9%) 96 (6.2%)

*Study vaccine given at ≥28 through 36 weeks and 0 days gestation. Data from Table 1 among infants for whom the protocol-mandated dating ultrasonography result was 

available for calculating gestational age.

1. Madhi SA, Polack FP, Piedra PA, et al. Respiratory syncytial virus vaccination during pregnancy and effects in infants. N Engl J Med 2020;383:426-39. DOI: 

10.1056/NEJMoa1908380
20

Preterm birth and low birth weight outcomes in 

maternal RSV vaccine clinical trials: Pfizer RSVpreF 

vaccine phase 3 trial data

*Confidence intervals not reported for these estimates. 

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)

RSVpreF vaccine group

N=3,568

Placebo group

N=3,558

Preterm birth (<37 weeks) 5.7% (95% CI: 4.9%, 6.5%) 4.7% (95% CI: 4.1%, 5.5%)

Late preterm birth (≥34 to 

<37 weeks)

5.0%* 4.4%*

Low birth weight (≤2500g) 5.1% (95% CI: 4.4%, 5.8%) 4.4% (95% CI: 3.7%, 5.0%) 
21

Infant deaths in maternal RSV vaccine clinical trials: 

Pfizer RSVpreF vaccine phase 3 trial data

▪ Infant deaths (all-cause) through 24 months of age: 5 (0.1%) in the 

RSVpreF group vs 12 (0.3%) in placebo group

▪ Among infant deaths in the RSVpreF group

– 4 of 5 deaths were considered unrelated to the investigational product 

by FDA

– 1 death was in an infant with extreme prematurity (27 weeks) and 

prematurity-related complications, and FDA was unable to exclude 

possibility of relationship to investigational product

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)
22

Time from Vaccination to Birth Among Preterm and 

Term Births, Infant Participants, Safety Population: 

Pfizer RSVpreF vaccine phase 3 trial data

▪ Median gestational age at vaccination in trial was 31 weeks

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)
23

Subgroup analysis of gestational age at birth among 

live births by country income level: Pfizer RSVpreF

vaccine phase 3 trial data

▪ In high-income countries, preterm birth rate was 5.1% (126/2494) in 

RSVpreF recipients vs 5.1% (126/2484) placebo recipients

▪ Imbalance was most prominent in upper middle income countries: 7.5% 

(72/964) in RSVpreF recipients vs. 4.1% (39/961) in placebo recipients

Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document- FDA
24

Subgroup analysis of gestational age at birth among 

live births, South Africa and US: Pfizer RSVpreF vaccine 

phase 3 trial data

Trial was conducted in 18 countries. 

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

▪ In South Africa, preterm birth rate was 8.3% (39/469) in RSVpreF recipients 

vs 4.0% (19/471) placebo recipients

▪ In US, preterm birth rate was 5.7% (94/1654) in RSVpreF recipients vs. 5.3%

(87/1644) in placebo recipients
25

VRBPAC discussion regarding preterm births: Pfizer 

RSVpreF vaccine 

▪ An imbalance was seen in preterm births in both phase 2b and phase 3 

trials, but the imbalance was not statistically significant

▪ Preterm birth rate in trials was lower than background incidence rate of 

preterm birth (~10% in US), but the trial had multiple exclusion criteria 

selecting for a population at lower risk of preterm birth

▪ Trial was underpowered to detect a 20% relative increase in preterm birth

181st Meeting of the Vaccines and Related Biological Products Advisory Committee – YouTube

Preterm Birth | Maternal and Infant Health | Reproductive Health | CDC
26

VRBPAC discussion regarding preterm births: Pfizer 

RSVpreF vaccine (cont.)

▪ Imbalance was still present but less pronounced when comparing 

prevalence of low birth weight

▪ Most preterm births were late preterm (≥34 to <37 weeks)

▪ Most preterm births were >30 days after vaccination

▪ Preterm birth imbalance was most prominent in a single country, South 

Africa

▪ VRBPAC voted 14-0 that the data supported effectiveness of Pfizer 

maternal RSVpreF and voted 10-4 that data supported safety

181st Meeting of the Vaccines and Related Biological Products Advisory Committee - YouTube
27

Other considerations: Inflammatory neurologic events 

Pfizer RSVPreF Vaccine

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

▪ Within the main phase 3 trial for this product among adults ages ≥ 60 years (RENOIR) 

a potential neurologic safety signal was identified

▪ A total of 3 cases of potential inflammatory neurologic events were recorded among 

20,255 investigational vaccine recipients across all clinical trials. No cases were 

observed among placebo recipients.

https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2023-06-21-23/06-RSV-Adults-Melgar-508.pdf)
28

Other considerations: Inflammatory neurologic events 

Pfizer RSVPreF Vaccine (cont.)

▪ 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

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 
29

Benefits and Harms Pfizer Maternal RSVPreF Vaccine

▪ 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 

Minimal Small Moderate Large Varies Don’t know
30

Benefits and Harms Pfizer Maternal RSVPreF Vaccine

▪ How substantial are the undesirable anticipated effects?

– How substantial are the anticipated effects for:

• Serious adverse events in pregnant women 

• Reactogenicity (3+ or higher) in pregnant women 

• Serious adverse events in infants 

• Preterm birth 

Minimal Small Moderate Large Varies Don’t know

Minority Opinion
31

Benefits and Harms Pfizer Maternal RSVPreF Vaccine

▪ Do the desirable effects outweigh the undesirable effects?

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

undesirable effects?

Favors intervention (Pfizer Maternal RSVPreF 

Vaccine)

Favors comparison (No intervention)

Favors both

Favors neither

Unclear
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?
33

University of Iowa, RAND, and CDC Values Survey, 

December 21, 2022-January 2, 2023

▪ 523 participants

– Pregnancy status:*

• 58.1% currently pregnant

• 44.9% given birth in the last 12 months

– Race and Ethnicity:*

• 66.0% Non-Hispanic White 

• 16.5% Non-Hispanic Black

• 9.8% Hispanic

• 7.7% Other Race/Ethnicity

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

*Participants were able to select all applicable answer choices.

CDC and University of Iowa/RAND survey, unpublished
34

61% of respondents said they ‘definitely’ or ‘probably’ 

would get an RSV vaccine while pregnant

CDC and University of Iowa/RAND survey, unpublished
35

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

CDC and University of Iowa/RAND survey, unpublished
36

22% of respondents did not want any vaccines or were unsure about how 

many vaccines they would be willing to get in the same healthcare visit 

during pregnancy

Prefer not to say

0%

Unsure 

10%

No vaccines

12%

One vaccine

17%

Two vaccines

32%

Three vaccines

9%

Four vaccines

20%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

% of respondents (n=523)

CDC and University of Iowa/RAND survey, unpublished
37

Tdap vaccine coverage among pregnant women (n=838), 

by race and ethnicity — Internet Panel Survey, United 

States, April 2020 – April 2022 

Flu, Tdap, and COVID-19 Vaccination Coverage Among Pregnant Women – United States, April 2022 | FluVaxView | Seasonal Influenza (Flu) | CDC
38

Values

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

relative to undesirable effects?

No Probably No Probably Yes Yes Varies Don’t know
39

Values

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

much pregnant people value the main outcomes?

Important uncertainty or variability

Probably important uncertainty or variability

Probably not important uncertainty or variability

No important uncertainty or variability

No known undesirable outcomes

Minority Opinion
EtR Domain: Acceptability

Is the intervention acceptable to key stakeholders?
41

Maternity healthcare professionals survey—England, 

2019

▪ 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

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 38(9):p 944-951, September 2019. | DOI: 

10.1097/INF.0000000000002384
42

Acceptability

▪ Is RSV prevention with Pfizer maternal RSVPreF vaccine acceptable to 

key stakeholders?

No Probably No Probably Yes Yes Varies Don’t know
EtR Domain: Feasibility

Is the intervention feasible to implement?
44

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

ShowLabeling.aspx (pfizer.com) and Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Presentation- Bivalent RSV Prefusion F 

Vaccine for Maternal Immunization to Protect Infants (fda.gov)
45

Timing of RSVPreF vaccination during pregnancy

▪ Trial dosing was between 24 through 36 weeks gestation

▪ Median gestational age at vaccination in phase 3 trial was 31 weeks1

▪ Administration of maternal RSVPreF vaccine during regularly scheduled 

prenatal visits and bundling with recommended screening tests and 

other recommended vaccinations could also improve feasibility

– Tdap recommended every pregnancy, preferably during the early part 

of gestational weeks 27 through 362

– Glucose challenge test recommended at 26-28 weeks gestation3

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

3. US HHS OASH, https://www.womenshealth.gov/pregnancy/youre-pregnant-now-what/prenatal-care-andtests#:~:text=Typically%2C%20routine%20checkups%20occur%3A,for%20weeks%2036%20to%20birth
46

Efficacy against medically attended RSV-associated 

lower respiratory tract disease by gestational age at 

vaccination 

Subgroup Gestational Age at 

Vaccination

RSVpreF 

(N= 3495) 

n

RSVpreF 

(N= 3495) 

# cases (%)

Placebo 

(N=3480)

n

Placebo 

(N=3480) 

# cases (%) VE (%) (95% CI)

Interim analysis at 180 days -- -- -- -- --

≥24 weeks to <28 weeks 890 22 (2.5) 866 27 (3.1) 20.7 (-44.6, 57.0)

≥28 weeks to <32 weeks 1030 11 (1.1) 1070 35 (3.3) 67.4 (34.2, 85.0)

≥32 weeks to ≤36 weeks 1572 24 (1.5) 1539 55 (3.6) 57.3 (29.8, 74.7)

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)

Source: adapted from Pfizer 1008 CSR

Abbreviations: RSV= respiratory syncytial virus; VE= vaccine efficacy; CI= confidence interval

Note: this subgroup analysis did not appear in the FDA Briefing Document 
47

Potential considerations for timing of RSV vaccine 

dosing during the year

▪ RSV vaccine dosing could be implemented for pregnant people as a 

seasonal campaign or year-round 

▪ Year-round dosing

– Simplify implementation and potentially increase vaccine uptake

– Protect infants in the event of atypical RSV seasonality

– Is less cost-effective

▪ Limited benefit for doses given during March-May changes benefit/risk 

calculation
48

Potential considerations for timing of RSV vaccine 

dosing during the year (cont.)

▪ Some U.S. jurisdictions have different or less predictable RSV 

seasonality, and recommendations for RSV vaccine dosing in those 

jurisdictions would need to account for that

– Tropical climates: parts of Florida, Puerto Rico, U.S. Virgin Islands, 

Hawaii, Guam, and U.S.-affiliated Pacific Islands

– Alaska: RSV seasonality is less predictable, and the duration of RSV 

activity is often longer than the national average
49

Simultaneous administration of RSV vaccines in 

pregnant people

▪ Pregnant people may potentially be eligible to receive RSV, Tdap, 

COVID-19, and influenza vaccines at same visit

▪ No available data on simultaneous administration of RSVpreF vaccine in 

pregnant people and limited data in non-pregnant people

▪ According to CDC’s immunization general best practices, ageappropriate vaccinations can be administered simultaneously, with two 

specific exceptions1,2

1. In persons with anatomic or functional asplenia and/or HIV infection, quadrivalent meningococcal conjugate vaccine (MCV4)-D (MenACWY-D, Menactra) and 

pneumococcal conjugate vaccine (PCV)13 (PCV13, Prevnar 13) should not be administered simultaneously. In patients recommended to receive both PCV13 and PPSV23, 

the 2 vaccines should not be administered simultaneously. ACIP Timing and Spacing Guidelines for Immunization | CDC
50

Available data on simultaneous administration with 

Pfizer RSVpreF vaccine

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

coadministration of Tdap and Pfizer RSVpreF 1

– Coadministration of Tdap and Pfizer RSVpreF led to decreased immune response to 

pertussis components (i.e. non-inferiority criteria were not met)

▪ Phase 3 study in non-pregnant adults ages ≥65 years on coadministration of 

RSVpreF and adjuvanted seasonal quadrivalent influenza vaccine2

– Non-inferiority criteria were met for antibody titers against all 4 influenza strains, 

as well as RSV-A and RSV-B

▪ No safety concerns in either trial

▪ Neither trial evaluated efficacy (not powered)

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

Vaccine, The Journal of Infectious Diseases, Volume 225, Issue 12, 15 June 2022, Pages 2077–2086, https://doi.org/10.1093/infdis/jiab505

2. Safety and Immunogenicity of RSVpreF Coadministered With SIIV in Adults ≥65 Years of Age - Full Text View - ClinicalTrials.gov
51

Pertussis immunogenicity and co-administration in 

adolescents and adults

▪ There is no accepted correlate of protection for pertussis vaccination

– In the absence of a correlate of protection, non-inferiority is used to assess 

immunogenicity of co-administration

– Clinical significance of failing to meet non-inferiority for pertussis is unclear 

▪ Some studies in adolescents and adults looking at Tdap coadministration 

with other vaccines, including meningococcal and influenza vaccines, failed 

to demonstrate non-inferiority against at least one pertussis antibody, but 

coadministration is still recommended

▪ Unclear how this might impact protection against pertussis from maternal 

Tdap when co-administered with RSVpreF

Liang JL, Tiwari T, Moro P, et al. Prevention of Pertussis, Tetanus, and Diphtheria with Vaccines in the United States: Recommendations of the Advisory Committee on 

Immunization Practices (ACIP). MMWR Recomm Rep 2018;67(No. RR-2):1–44. DOI: http://dx.doi.org/10.15585/mmwr.rr6702a1external icon
52

Place of Flu, Tdap, COVID-19 Vaccination among 

Pregnant Women, United States, Internet Panel 

Survey, April 2022

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

“Other place” includes other medical or non-medical place, including school or special site for COVID-19 vaccination
53

Availability of vaccines to pregnant people by practice 

type

▪ Survey of health care providers conducted in Fall 2022

Provider type (%)

Total 

(n=1,538)

Family 

Practitioner/ 

Internist Pediatrician OB/GYN NP/PA

Tdap 72% 73% 79% 74% 58%

COVID-19 53% 56% 66% 40% 49%

Influenza 81% 85% 83% 74% 67%

Ob/Gyn = Obstetrician-Gynecologist; NP/PA: Nurse Practitioner or Physician’s Assistant 

Unpublished data, Fall 2022 DocStyles

Proportion of practices that offer or administer vaccinations on site to pregnant patients
54

Feasibility

▪ Is Pfizer Maternal RSVPreF vaccine feasible to implement among 

pregnant people at 24-36 weeks gestation?

No Probably No Probably Yes Yes Varies Don’t know

Minority Opinion
EtR Domain: Resource Use

Is the intervention a reasonable and efficient allocation of resources?
56

Summary of Economic Analysis of RSVPreF in Pediatric 

Populations

▪ RSVPreF has the potential to be cost-effective

– Base case ICER: $214,087/QALY 

▪ Results sensitive to:

– Rate of prematurity 

– Cost per dose

– Efficacy

– QALYs lost

– Timing of vaccination: year-round vs seasonal (e.g., June-February)

ICER: Incremental cost-effectiveness ratio; QALY: Quality-adjusted life year
57

Resource Use

▪ Is Pfizer Maternal RSVPreF vaccine use among pregnant people at 24–

36 weeks gestation a reasonable and efficient allocation of resources?

No Probably No Probably Yes Yes Varies Don’t know
EtR Domain: Equity

What would be in the impact of the intervention on health equity?
59

Population-based hospitalization rates among infants <6 months 

old with laboratory-confirmed RSV by race and ethnicity, RSV-NET, 

2018–2019 to 2021–2022

▪ Hospitalization rates among infants <6 months old differ by race and ethnicity but vary by 

season 

▪ Rates were not adjusted for RSV testing practices and thus may underrepresent RSV 

hospitalization rates but should not affect distributions by race and ethnicity 

RSV-NET: unpublished data. Surveillance was conducted from October–April for the 2018–19 and 2019–20 seasons, October–September for the 2020–21 season, and October–

September excluding May–June for the 2021–22 season. Rates were not adjusted for RSV testing practices; testing practices may differ by racial and ethnic groups and may have 

changed over time. Black, White, Asian/Pacific Islander children were categorized as non-Hispanic; Hispanic children could be of any race. 

0

2

4

6

8

10

12

14

16

2018–2019 2019–2020 2020–2021 2021–2022

Rate per 1,000 population

Non-Hispanic Black Hispanic Non-Hispanic White Non-Hispanic Asian/Pacific Islander
60

0

1

2

3

4

5

6

7

2018–2019 2019–2020 2020–2021 2021–2022

Rate per 1,000 population

Non-Hispanic Black Hispanic Non-Hispanic White Non-Hispanic Asian/Pacific Islander

Population-based ICU admission rates among infants <6 months 

old with laboratory-confirmed RSV by race and ethnicity, RSVNET, 2018–2019 to 2021–2022

RSV-NET: unpublished data. Surveillance was conducted from October–April for the 2018–19 and 2019–20 seasons, October–September for the 2020–21 season, and October–

September excluding May–June for the 2021–22 season. Rates were not adjusted for RSV testing practices; testing practices may differ by racial and ethnic groups and may have 

changed over time. Black, White, and Asian/Pacific Islander children were categorized as non-Hispanic; Hispanic children could be of any race.

ICU admission rates among Non-Hispanic Black infants <6 months 

old were 1.2–1.6x higher than among Non-Hispanic White infants
61

Seasonal rate of RSV-associated hospitalizations per 

1,000 children among American Indian and Alaska 

Native children <5 years of age, Nov 2019- May 2020 

(SuNA)*

*Hartman et al, RSV2022 12th International Symposium, Belfast 9/29/2022-10/2/2022; Atwell et al. RSV among American Indian and Alaska Native children: 2019-20 

(manuscript in press) SuNA = RSV Surveillance among Native American Persons

**Incidence of RSV-associated hospitalization in 2019-2020 included for comparison. NVSN = New Vaccine Surveillance Network.

Age Chinle, Arizona Whiteriver, 

Arizona 

Anchorage, Alaska Yukon-Kuskokwim 

Delta, Alaska

NVSN** for 

comparison

0-5 Months 83.0 (52.0, 132.5) 70.4 (36.3, 136.6) 35.7 (20.4, 62.6) 132.3 (98.2, 178.1) 21.6 (20.0, 23.3)

6-11 Months 61.6 (35.9, 105.8) 90.1 (50.0, 162.3) 0.0 (0.0, 10.8) 91.6 (64.0, 131.0) 8.2 (7.1, 9.3)

0-11 Months 71.8 (50.4, 102.4) 80.6 (51.9, 125.2) 19.2 (11.2, 33.0) 112.2 (89.3, 141.0) 14.9 (13.9, 16.0)

12-23 Months 42.1 (27.2, 65.3) 38.7 (22.0, 68.1) 15.6 (8.7, 27.7) 26.4 (16.6, 41.8) 4.5 (3.9, 5.2)

24-59 Months 10.9 (6.8, 17.4) 8.2 (4.2, 16.0) 1.1 (0.3, 3.8) 5.9 (3.2, 10.9) 1.2 (1.2, 1.5)

0-59 Months 27.2 (21.4, 34.4) 25.4 (18.7, 34.5) 7.7 (5.3, 11.1) 32.7 (26.9, 39.7) 4.6 (4.3, 4.8)
62

Insurance coverage for vaccinations among pregnant 

people

▪ All ACIP-recommended vaccinations are covered without cost-sharing for adults in 

the Affordable Care Act (ACA) adult group who receive all essential health benefits1

▪ Beginning on October 1, 2023, coverage of all approved ACIP-recommended adult 

vaccines and vaccine administration, without cost sharing, will be mandatory for 

both Medicaid and the Children’s Health Insurance Program under section 11405 of 

the Inflation Reduction Act (IRA) (Pub. L. 117-169). 

▪ Currently, most state Medicaid agencies cover at least some ACIP-recommended 

adult immunizations for those not subject to essential health benefits, but may not 

cover all recommended vaccines.

1 Quality of Care Vaccines | Medicaid
63

Medicaid coverage among pregnant people

▪ By federal law, all states provide Medicaid coverage for pregnancyrelated services to pregnant women with incomes up to 138% of the 

federal poverty level1

▪ In 2020, 42.0% of mothers had Medicaid at the time of birth2

▪ In 2020, about 1 in 9 (11.6%) women of childbearing age (aged 15-44 

years) was uninsured in the United States3

1 Medicaid Coverage for Women | KFF

2 Medicaid coverage of births: United States, 2020 | PeriStats | March of Dimes

3 Uninsured women: United States, 2010-2020 | PeriStats | March of Dimes
64

Equity

▪ What would be the impact of Pfizer Maternal RSVPreF vaccine on 

health equity?

Reduced

Probably reduced

Probably no impact

Probably increased

Increased

Varies

Don’t know
Summary
66

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? Moderate to large

How substantial are the undesirable anticipated effects? Small vs Don’t Know

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

Values Does the target population feel the desirable effects are large 

relative to the undesirable effects?

Probably Yes

Is there important variability in how patients value the 

outcome?

Probably important 

uncertainty or variability 

Acceptability Is the intervention acceptable to key stakeholders? Probably yes or Yes

Feasibility Is the intervention feasible to implement? Probably yes 

Resource Use Is the intervention a reasonable and efficient allocation of 

resources?

Probably yes 

Equity What would be in the impact of the intervention on health 

equity?

Probably increased 
67

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

Minority Opinion
68

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

Minority Opinion
69

Summary of WG interpretations 

▪ Efficacious vaccine that can prevent RSV lower respiratory tract infection in 

young infants

▪ WG expressed concern that the Pfizer trial was underpowered to detect a 

20% difference in preterm births between vaccine and placebo recipients

▪ Interpretation of these overarching themes varied:

– Some members of the WG expressed concern that the data were insufficient to 

determine the safety of this vaccine 

– Others stressed this vaccine can provide benefit by preventing RSV lower 

respiratory tract infection in infants and the difference in preterm births was 

not statistically significant
70

Summary of WG interpretations (cont.) 

▪ Imbalance in preterm birth was most prominent in a single country, South 

Africa

▪ Imbalance in preterm births was not seen in high-income countries

▪ Imbalance was still present but less pronounced when comparing 

prevalence of low birth weight

▪ Most preterm births were >30 days after vaccination
71

Summary of WG interpretations (cont.) 

▪ WG discussed considering a narrower recommended dosing window

– Some expressed support for starting dosing at a later gestational age within 

24–36-week window used in the trial as this could mitigate potential risk of 

early preterm birth until additional safety data are available

– Others expressed concern that this could leave preterm infants who are at 

higher risk of severe RSV disease unprotected

▪ Aligning RSVpreF vaccine dosing during pregnancy with Tdap 

administration could improve feasibility

▪ All WG members endorsed the importance of post-introduction vaccine 

safety monitoring
72

ACIP Policy Question

▪ Should vaccination with Pfizer RSVPreF vaccine (120μg antigen, 1 dose 

IM given 24–36 weeks gestation) be recommended for pregnant people 

to prevent RSV disease in infants?
Summary of proposed clinical 

considerations for use of Pfizer RSVpreF

vaccine during pregnancy
74

Proposed clinical considerations: Timing of dosing 

during pregnancy and simultaneous administration

▪ Proposed dosing interval for RSVpreF vaccine is 24–36 weeks (aligned with 

trials)

▪ Healthcare providers could consider aligning RSVpreF vaccine dosing during 

pregnancy with Tdap administration for feasibility of implementation 

▪ RSVpreF vaccine can be administered with other recommended vaccines 

(e.g., influenza, COVID-19) without regards to timing, including 

simultaneous vaccination on same clinic day
75

Proposed clinical considerations: Timing of dosing 

during the year

▪ RSVpreF vaccine should be offered to pregnant people during JuneFebruary in the continental United States 

▪ Healthcare providers can consider offering RSVpreF vaccine year-round 

– For ease of implementation

– If RSV seasonality is unpredictable

– In jurisdictions with different RSV seasonality than continental U.S.
76

Proposed clinical considerations: Additional vaccine 

doses in subsequent pregnancies

▪ Currently there are no data available on

– Efficacy of the first lifetime dose during subsequent pregnancies

– Safety of additional doses given in subsequent pregnancies

▪ WG felt that it was too early 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
77

Acknowledgements 

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
78

Note

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.
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.
Extra slides for GRADE
Centers for Disease Control and Prevention

Grading of Recommendations, Assessment, 

Development, and Evaluation (GRADE): 

Pfizer Maternal RSVPreF Vaccine 

Update: May 19, 2023
82

Evidence Retrieval, conducted as of April 10, 2023

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)

*Medline (OVID), Embase (OVID), Cochrane Library, CINAHL (EbscoHost), Scopus, clinicaltrials.gov
83

▪ 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.

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.

GRADE Evidence Type
84

GRADE Evidence Type

▪ 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.

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.
Benefits
86

Outcome 1: Medically attended RSV-associated lower 

respiratory tract infection in infants (n=1 study)

▪ 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

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.
87

Outcome 1: Medically attended RSV-associated lower 

respiratory tract infection in infants (n=1 study)

▪ 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

▪ Positive validated RT-PCR in central laboratory

▪ Confirmed by endpoint adjudication committee (EAC)

SpO2= Peripheral capillary oxygen saturation 
88

Outcome 1: Medically attended RSV-associated lower 

respiratory tract infection in infants (n=1 study)

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)

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 This outcome did not meet success criterion using manufacturer calculated VE (lower bound of CI was <20%) 
89

Outcome 1: Severe Medically attended RSV-associated 

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

▪ 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

▪ Positive validated RT-PCR in central laboratory

▪ Confirmed by endpoint adjudication committee (EAC)

SpO2= Peripheral capillary oxygen saturation 
90

Outcome 1: Severe Medically attended RSV-associated 

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

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)

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).
91

GRADE: Medically attended RSV-associated lower 

respiratory infection in infants (n=1 study)

▪ Measures of effect

– Relative Risk: 0.487 (0.332, 0.706)

– Absolute Risk1: 17 fewer per 1,000 (10 to 22 fewer); NNV: 59 (45, 100)

– Absolute Risk2: 119 fewer per 1,000 (68 to 154 fewer); NNV: 8 (6, 15)

– Absolute Risk3: 56 fewer per 1,000 (32 to 73 fewer); NNV: 18 (14, 31)

▪ Concerns in certainty assessment: None

▪ Evidence type: High

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 LRTI. 

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

NNV= Number needed to vaccinate
92

Outcome 2: Hospitalization for RSV-associated lower 

respiratory tract infection in infants (n=1 study)

▪ Phase 3 RCT, MATISSE1

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

▪ Confirmed by endpoint adjudication committee (EAC)

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.
93

Outcome 2: Hospitalization for RSV-associated lower 

respiratory tract infection in infants (n=1 study)

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)

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%) 
94

GRADE: Hospitalization for RSV-associated lower 

respiratory tract infection in infants (n=1 study)

▪ Measures of effect

– Relative risk: 0.432 (0.193, 0.899)

– Absolute risk1: 7 fewer per 1,000 (1 to 10 fewer); NNV: 143 (100, 1,000)

– Absolute risk2: 11 fewer per 1,000 (2 to 15 fewer); NNV: 91 (67, 500) 

▪ 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

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) 
95

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

studies)

▪ 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

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
96

Outcome 6: All-cause medically attended lower 

respiratory tract infection in infants (n=1 study)

▪ 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

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.

SpO2= Peripheral capillary oxygen saturation 
97

Outcome 6: All-cause medically attended lower 

respiratory tract infection in infants (n=1 study)

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)

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 (lower bound of CI was <0%) 
98

GRADE: All-cause medically attended lower respiratory 

tract infection in infants (n=1 study)

▪ Measures of effect

– Relative risk: 0.975 (0.806, 1.179)

– Absolute risk*: 3 fewer per 1,000 (22 fewer to 21 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

*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.
Harms
100

Outcome 8: Serious adverse events in pregnant people 

(n=2 studies)

▪ 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)
101

Outcome 8: Serious adverse events in pregnant people 

(n=2 studies)

101

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.

Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document- FDA
102

GRADE: Serious adverse events in pregnant people 

(n=2 studies)

▪ Measures of effect

– Relative risk: 1.06 (0.95, 1.17)

– Absolute risk*: 9 more per 1,000 (8 fewer to 26 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

*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.
103

Outcome 9: Reactogenicity (grade 3+) in pregnant 

people (n=2 studies)

▪ 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
104

Outcome 9: Reactogenicity (grade 3+) in pregnant 

people 

104

Trial Outcome Events/Vaccine

(n/N)

Events/Placebo

(n/N)

Relative Risk (95% CI)

Phase 3 Local events (grade 3+) 11/3660 (0.3%) 0/3639 (0%) 22.87 (1.35, 387.94)

Systemic events (grade 3+) 83/3663 (2.3%) 83/3640 (2.3%) 0.94 (0.70, 1.28)

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. 
105

Outcome 9: Reactogenicity (grade 3+) in pregnant 

people (n=2 studies)

▪ Measures of effect

– Relative risk: 0.97 (0.72, 1.31)

– Absolute risk*: 1 fewer per 1,000 (6 fewer to 7 more)

▪ Concerns in certainty assessment: 

– Serious concern for indirectness as this data only includes systemic 

reactions 

▪ Evidence type: Moderate

*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.
106

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

studies)

▪ 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
107

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

studies)

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.

Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document- FDA
108

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

▪ Measures of effect

– Relative risk: 1.01 (0.91, 1.11)

– Absolute risk*: 2 more per 1,000 (16 fewer to 19 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

*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.
109

Outcome 11: Preterm births (n=2 studies)

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

from manufacturer)

– Gestational age at birth <37 weeks and <34 weeks
110

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

RSVpreF vaccine

110

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)

*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
111

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

RSVpreF vaccine

▪ Measures of effect

– Relative risk: 1.20 (0.99, 1.46)

– Absolute risk*: 9 more per 1,000 (from 0 fewer to 22 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

▪ Evidence type: Low

*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.
GRADE additional slides
113

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 (eg, 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 (eg, 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 (eg, 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.
114

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.
115

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.
116

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.
117

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 Engl J Med. 2023 Apr 5. doi: 

10.1056/NEJMoa2216480.
118

Table 1. Demographics of phase 3 trial

118

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.
119

Severity scale for local reactions and systemic events 

(maternal participants)

119

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.
120

Studies Included in the Review of Evidence

Last name first author, 

Publication year

Study design Country Age 

mean 

(SD)

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
121

Summary of Studies Reporting Outcome 1: Medically attended 

RSV-associated lower respiratory infection in infants 

Last name 

first author, 

Publication 

year

Age 

mean 

(SD)

N 

intervention

N 

comparison

Comparator 

Vaccine

Absolute 

difference/effect 

estimate (99.58% 

CI)

Study 

limitations 

(Risk of Bias)

Kampmann B, 

et al.

29.0

(5.7)

3495 3480 Placebo 17 fewer per 

1,000 (10 to 22 

fewer)

None
122

Summary of Studies Reporting Outcome 2: Hospitalization for 

RSV-associated lower respiratory tract infection in infants 

Last name first 

author, 

Publication 

year

Age 

mean 

(SD)

N 

intervention

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 7 fewer per 1,000 

(1 to 10 fewer)

None
123

Summary of Studies Reporting Outcome 5: RSVassociated death in infants 

Last name first 

author, 

Publication 

year

Age 

mean 

(SD)

N 

intervention

N 

comparison

Comparator 

Vaccine

Absolute 

difference/effe

ct 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

N/A

Phase 2b RCT, 

unpublished

18-49 

(range)

114 116 Placebo Not estimable 

0 deaths in trial

N/A
124

Summary of Studies Reporting Outcome 6: All cause medically 

attended lower respiratory tract infection in infants 

Last name first 

author, 

Publication 

year

Age 

mean 

(SD)

N 

intervention

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 3 fewer per 1,000 

(22 fewer to 21 

more)

None
125

Summary of Studies Reporting Outcome 8: Serious 

adverse events in pregnant people 

Last name first 

author, 

Publication 

year

Age 

mean 

(SD)

N 

intervention

N 

comparison

Comparator 

Vaccine

Absolute 

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
126

Summary of Studies Reporting Outcome 9: 

Reactogenicity (grade 3+) in pregnant people 

Last name first 

author, 

Publication 

year

Age 

mean 

(SD)

N 

interventio

n

N 

comparison

Comparator 

Vaccine

Absolute 

difference/effect 

estimate

Study 

limitations 

(Risk of Bias)

Kampmann B, 

et al.

29.0 

(5.7)

3663 3640 Placebo RR: 0.94 (0.70, 

1.28)

None

Phase 2b RCT 27.1

(5.2)

114 117 Placebo RR: 0.51 (0.10, 

2.75)

None
127

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

Absolute 

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
128

Summary of Studies Reporting Outcome 11: Preterm 

birth

Last name first 

author, Publication 

year

Age mean 

(SD)

N intervention N comparison Comparator 

Vaccine

Absolute 

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
129

Grade Summary of Findings Table- Benefits

129

No of 

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

Absolute

(95% 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 

(0.332, 

0.706)

17 fewer 

per 1,000 

(10 to 22 

fewer)

Critical High

23.1% 119 fewer 

per 1,000 

(68 to 154 

fewer)

11.0% 56 fewer 

per 1,000 

(32 to 73 

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 

(0.193, 

0.899)

7 fewer per 

1,000 (1 to 

10 fewer)

Critical Moderate

1.9% 11 fewer 

per 1,000 (2 

to 15 fewer)

All-cause medically attended lower respiratory infection in infants

1 Randomized 

studies

Not serious Not serious Not serious Serious None 392/3495 

(11.2%)

402/3480 

(11.6%)

0.97 (0.85, 

1.11)

3 fewer per 

1,000 (22 

fewer to 21 

more)

Important Moderate
130

Grade Summary of Findings Table- Harms

130

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

Not serious Serious None 605/3797 

(15.9%)

572/3792 

(15.1%)

1.06 

(0.95, 

1.17)

9 more per 

1,000 (8 

fewer to 26 

more)

Critical Moderate

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)

1 fewer per 

1,000 (6 

fewer to 7 

more)

Important Moderate

Serious adverse events in infants

2 Randomized 

studies

Not 

serious

Not 

serious

Not serious Serious None 625/3568 

(17.5%)

623/3558 

(17.5%)

1.01 

(0.91, 

1.11)

2 more per 

1,000 (16 

fewer to 19 

more)

Critical Moderate

Preterm birth

2 Randomized 

studies

Not 

serious

Not 

serious

Not serious Very 

serious

None 207/3683 

(5.6%)

172/3675 

(4.7%)

1.20 

(0.99, 

1.46)

9 more per 

1,000 (0 

fewer to 22 

more)

Critical Low