Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants

MATISSE Study Group

doi:10.1056/NEJMoa2216480

Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants

MATISSE Study Group

Department of Clinical Medicine - Department of Infectious Diseases

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

486 Citations (Scopus)

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Abstract

BACKGROUND: Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)-associated lower respiratory tract illness in newborns and infants is uncertain.

METHODS: In this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks' gestation to receive a single intramuscular injection of 120 μg of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine or placebo. The two primary efficacy end points were medically attended severe RSV-associated lower respiratory tract illness and medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth. A lower boundary of the confidence interval for vaccine efficacy (99.5% confidence interval [CI] at 90 days; 97.58% CI at later intervals) greater than 20% was considered to meet the success criterion for vaccine efficacy with respect to the primary end points.

RESULTS: At this prespecified interim analysis, the success criterion for vaccine efficacy was met with respect to one primary end point. Overall, 3682 maternal participants received vaccine and 3676 received placebo; 3570 and 3558 infants, respectively, were evaluated. Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group (vaccine efficacy, 81.8%; 99.5% CI, 40.6 to 96.3); 19 cases and 62 cases, respectively, occurred within 180 days after birth (vaccine efficacy, 69.4%; 97.58% CI, 44.3 to 84.1). Medically attended RSV-associated lower respiratory tract illness occurred within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group (vaccine efficacy, 57.1%; 99.5% CI, 14.7 to 79.8); these results did not meet the statistical success criterion. No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age. The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively).

CONCLUSIONS: RSVpreF vaccine administered during pregnancy was effective against medically attended severe RSV-associated lower respiratory tract illness in infants, and no safety concerns were identified. (Funded by Pfizer; MATISSE ClinicalTrials.gov number, NCT04424316.).

Original language	English
Journal	The New England Journal of Medicine
Volume	388
Issue	16
Pages (from-to)	1451-1464
Number of pages	14
ISSN	0028-4793
DOIs	https://doi.org/10.1056/NEJMoa2216480
Publication status	Published - 20 Apr 2023

Keywords

Antibodies, Viral
Communicable Diseases/therapy
Double-Blind Method
Female
Humans
Infant
Infant, Newborn
Injections, Intramuscular
Pregnancy
Respiratory Syncytial Virus Infections/epidemiology
Respiratory Syncytial Virus Vaccines/administration & dosage
Respiratory Syncytial Viruses
Respiratory Tract Infections/epidemiology
Treatment Outcome
Vaccination/adverse effects
Vaccine Efficacy
Vaccines, Combined/administration & dosage
Pediatrics
Childhood Diseases
Infectious Disease
Neonatology
Infectious Disease General
Vaccines
Viral Infections
Obstetrics/Gynecology General
Global Health
Obstetrics/Gynecology
Pediatrics General

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10.1056/NEJMoa2216480

Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in InfantsFinal published version, 950 KB

Cite this

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title = "Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants",

abstract = "BACKGROUND: Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)-associated lower respiratory tract illness in newborns and infants is uncertain.METHODS: In this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks' gestation to receive a single intramuscular injection of 120 μg of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine or placebo. The two primary efficacy end points were medically attended severe RSV-associated lower respiratory tract illness and medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth. A lower boundary of the confidence interval for vaccine efficacy (99.5% confidence interval [CI] at 90 days; 97.58% CI at later intervals) greater than 20% was considered to meet the success criterion for vaccine efficacy with respect to the primary end points.RESULTS: At this prespecified interim analysis, the success criterion for vaccine efficacy was met with respect to one primary end point. Overall, 3682 maternal participants received vaccine and 3676 received placebo; 3570 and 3558 infants, respectively, were evaluated. Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group (vaccine efficacy, 81.8%; 99.5% CI, 40.6 to 96.3); 19 cases and 62 cases, respectively, occurred within 180 days after birth (vaccine efficacy, 69.4%; 97.58% CI, 44.3 to 84.1). Medically attended RSV-associated lower respiratory tract illness occurred within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group (vaccine efficacy, 57.1%; 99.5% CI, 14.7 to 79.8); these results did not meet the statistical success criterion. No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age. The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively).CONCLUSIONS: RSVpreF vaccine administered during pregnancy was effective against medically attended severe RSV-associated lower respiratory tract illness in infants, and no safety concerns were identified. (Funded by Pfizer; MATISSE ClinicalTrials.gov number, NCT04424316.).",

keywords = "Antibodies, Viral, Communicable Diseases/therapy, Double-Blind Method, Female, Humans, Infant, Infant, Newborn, Injections, Intramuscular, Pregnancy, Respiratory Syncytial Virus Infections/epidemiology, Respiratory Syncytial Virus Vaccines/administration & dosage, Respiratory Syncytial Viruses, Respiratory Tract Infections/epidemiology, Treatment Outcome, Vaccination/adverse effects, Vaccine Efficacy, Vaccines, Combined/administration & dosage, Pediatrics, Childhood Diseases, Infectious Disease, Neonatology, Infectious Disease General, Vaccines, Viral Infections, Obstetrics/Gynecology General, Global Health, Obstetrics/Gynecology, Pediatrics General",

author = "Beate Kampmann and Madhi, {Shabir A} and Iona Munjal and Sim{\~o}es, {Eric A F} and Pahud, {Barbara A} and Conrado Llapur and Jeffrey Baker and {P{\'e}rez Marc}, Gonzalo and David Radley and Emma Shittu and Julia Glanternik and Hasra Snaggs and James Baber and Philip Zachariah and Barnabas, {Shaun L} and Merlin Fausett and Tyler Adam and Nicole Perreras and {Van Houten}, {Marlies A} and Anu Kantele and Li-Min Huang and Bont, {Louis J} and Takeo Otsuki and Vargas, {Sergio L} and Joanna Gullam and Bruce Tapiero and Stein, {Renato T} and Polack, {Fernando P} and Zar, {Heather J} and Staerke, {Nina B} and {Duron Padilla}, Mar{\'i}a and Richmond, {Peter C} and Kenneth Koury and Katherine Schneider and Kalinina, {Elena V} and David Cooper and Jansen, {Kathrin U} and Anderson, {Annaliesa S} and Swanson, {Kena A} and Gruber, {William C} and Alejandra Gurtman and {MATISSE Study Group}",

note = "Copyright {\textcopyright} 2023 Massachusetts Medical Society.",

year = "2023",

month = apr,

day = "20",

doi = "10.1056/NEJMoa2216480",

language = "English",

volume = "388",

pages = "1451--1464",

journal = "The New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachussetts Medical Society",

number = "16",

}

TY - JOUR

T1 - Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants

AU - Kampmann, Beate

AU - Madhi, Shabir A

AU - Munjal, Iona

AU - Simões, Eric A F

AU - Pahud, Barbara A

AU - Llapur, Conrado

AU - Baker, Jeffrey

AU - Pérez Marc, Gonzalo

AU - Radley, David

AU - Shittu, Emma

AU - Glanternik, Julia

AU - Snaggs, Hasra

AU - Baber, James

AU - Zachariah, Philip

AU - Barnabas, Shaun L

AU - Fausett, Merlin

AU - Adam, Tyler

AU - Perreras, Nicole

AU - Van Houten, Marlies A

AU - Kantele, Anu

AU - Huang, Li-Min

AU - Bont, Louis J

AU - Otsuki, Takeo

AU - Vargas, Sergio L

AU - Gullam, Joanna

AU - Tapiero, Bruce

AU - Stein, Renato T

AU - Polack, Fernando P

AU - Zar, Heather J

AU - Staerke, Nina B

AU - Duron Padilla, María

AU - Richmond, Peter C

AU - Koury, Kenneth

AU - Schneider, Katherine

AU - Kalinina, Elena V

AU - Cooper, David

AU - Jansen, Kathrin U

AU - Anderson, Annaliesa S

AU - Swanson, Kena A

AU - Gruber, William C

AU - Gurtman, Alejandra

AU - MATISSE Study Group

PY - 2023/4/20

Y1 - 2023/4/20

N2 - BACKGROUND: Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)-associated lower respiratory tract illness in newborns and infants is uncertain.METHODS: In this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks' gestation to receive a single intramuscular injection of 120 μg of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine or placebo. The two primary efficacy end points were medically attended severe RSV-associated lower respiratory tract illness and medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth. A lower boundary of the confidence interval for vaccine efficacy (99.5% confidence interval [CI] at 90 days; 97.58% CI at later intervals) greater than 20% was considered to meet the success criterion for vaccine efficacy with respect to the primary end points.RESULTS: At this prespecified interim analysis, the success criterion for vaccine efficacy was met with respect to one primary end point. Overall, 3682 maternal participants received vaccine and 3676 received placebo; 3570 and 3558 infants, respectively, were evaluated. Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group (vaccine efficacy, 81.8%; 99.5% CI, 40.6 to 96.3); 19 cases and 62 cases, respectively, occurred within 180 days after birth (vaccine efficacy, 69.4%; 97.58% CI, 44.3 to 84.1). Medically attended RSV-associated lower respiratory tract illness occurred within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group (vaccine efficacy, 57.1%; 99.5% CI, 14.7 to 79.8); these results did not meet the statistical success criterion. No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age. The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively).CONCLUSIONS: RSVpreF vaccine administered during pregnancy was effective against medically attended severe RSV-associated lower respiratory tract illness in infants, and no safety concerns were identified. (Funded by Pfizer; MATISSE ClinicalTrials.gov number, NCT04424316.).

AB - BACKGROUND: Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)-associated lower respiratory tract illness in newborns and infants is uncertain.METHODS: In this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks' gestation to receive a single intramuscular injection of 120 μg of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine or placebo. The two primary efficacy end points were medically attended severe RSV-associated lower respiratory tract illness and medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth. A lower boundary of the confidence interval for vaccine efficacy (99.5% confidence interval [CI] at 90 days; 97.58% CI at later intervals) greater than 20% was considered to meet the success criterion for vaccine efficacy with respect to the primary end points.RESULTS: At this prespecified interim analysis, the success criterion for vaccine efficacy was met with respect to one primary end point. Overall, 3682 maternal participants received vaccine and 3676 received placebo; 3570 and 3558 infants, respectively, were evaluated. Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group (vaccine efficacy, 81.8%; 99.5% CI, 40.6 to 96.3); 19 cases and 62 cases, respectively, occurred within 180 days after birth (vaccine efficacy, 69.4%; 97.58% CI, 44.3 to 84.1). Medically attended RSV-associated lower respiratory tract illness occurred within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group (vaccine efficacy, 57.1%; 99.5% CI, 14.7 to 79.8); these results did not meet the statistical success criterion. No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age. The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively).CONCLUSIONS: RSVpreF vaccine administered during pregnancy was effective against medically attended severe RSV-associated lower respiratory tract illness in infants, and no safety concerns were identified. (Funded by Pfizer; MATISSE ClinicalTrials.gov number, NCT04424316.).

KW - Antibodies, Viral

KW - Communicable Diseases/therapy

KW - Double-Blind Method

KW - Female

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Injections, Intramuscular

KW - Pregnancy

KW - Respiratory Syncytial Virus Infections/epidemiology

KW - Respiratory Syncytial Virus Vaccines/administration & dosage

KW - Respiratory Syncytial Viruses

KW - Respiratory Tract Infections/epidemiology

KW - Treatment Outcome

KW - Vaccination/adverse effects

KW - Vaccine Efficacy

KW - Vaccines, Combined/administration & dosage

KW - Pediatrics

KW - Childhood Diseases

KW - Infectious Disease

KW - Neonatology

KW - Infectious Disease General

KW - Vaccines

KW - Viral Infections

KW - Obstetrics/Gynecology General

KW - Global Health

KW - Obstetrics/Gynecology

KW - Pediatrics General

UR - http://www.scopus.com/inward/record.url?scp=85158155775&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa2216480

DO - 10.1056/NEJMoa2216480

M3 - Journal article

C2 - 37018474

SN - 0028-4793

VL - 388

SP - 1451

EP - 1464

JO - The New England Journal of Medicine

JF - The New England Journal of Medicine

IS - 16

ER -

Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants

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