Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants.
Female
Humans
Infant
Infant, Newborn
Pregnancy
Antibodies, Viral
Communicable Diseases
/ therapy
Double-Blind Method
Injections, Intramuscular
Respiratory Syncytial Virus Infections
/ epidemiology
Respiratory Syncytial Virus Vaccines
/ administration & dosage
Respiratory Syncytial Viruses
Treatment Outcome
Vaccination
/ adverse effects
Vaccine Efficacy
Vaccines, Combined
/ administration & dosage
Respiratory Tract Infections
/ epidemiology
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
20 Apr 2023
20 Apr 2023
Historique:
medline:
21
4
2023
pubmed:
6
4
2023
entrez:
5
4
2023
Statut:
ppublish
Résumé
Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)-associated lower respiratory tract illness in newborns and infants is uncertain. 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. 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). 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.).
Sections du résumé
BACKGROUND
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
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
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
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.).
Identifiants
pubmed: 37018474
doi: 10.1056/NEJMoa2216480
doi:
Substances chimiques
Antibodies, Viral
0
Respiratory Syncytial Virus Vaccines
0
Vaccines, Combined
0
Banques de données
ClinicalTrials.gov
['NCT04424316']
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
1451-1464Investigateurs
Tyler Adam
(T)
Mario Aguilar
(M)
Khatija Ahmed
(K)
Mohamed Ahmed
(M)
Shinobu Akada
(S)
Ruben Aleman
(R)
Ai Anami
(A)
Evan Anderson
(E)
Marquita Anderson
(M)
Martti Antila
(M)
Eugene Athan
(E)
Jeffrey Baker
(J)
John Baker
(J)
Peyman Banooni
(P)
Shaun Barnabas
(S)
Elizabeth Barnett
(E)
José Luis Bartha Rasero
(JL)
Thomas Benfield
(T)
Dawn Black
(D)
Kitty Bloemenkamp
(K)
Bradford Brabec
(B)
Kent Branson
(K)
John Byron
(J)
Quito Carr
(Q)
Kristina Carter
(K)
Te-Fu Chan
(TF)
Peter Chen
(P)
Cheng-Hsun Chiu
(CH)
Robert Clifford
(R)
Dean Coonrod
(D)
Martín Darraidou
(M)
Elaine Davidson
(E)
Keith Davis
(K)
Angela Dawson
(A)
Pieter-Kees de Groot
(PK)
Koen Deurloo
(K)
Jaime Deville
(J)
Rachel DiTeresi
(R)
Pablo Doreski
(P)
Laura Downing
(L)
María Del Rosario Durón Padilla
(MDR)
Janet Englund
(J)
Merlin Fausett
(M)
María Del Pilar Fernández Fraile
(MDP)
Pedro Ferrand Miranda
(P)
Thea Kølsen Fischer
(TK)
Leon Fouche
(L)
Guillermo Galán
(G)
Cipiran Gheorghe
(C)
Jennifer Gilner
(J)
Vanna Gold
(V)
Bernard Gonik
(B)
Gary Gregerson
(G)
Rebecca Griffith
(R)
Sebastián Grinstein
(S)
Joanna Gullam
(J)
Abel Guzmán López
(A)
Erica Haake
(E)
Jeffrey Hamre
(J)
Robyn Hartvickson
(R)
Kazunari Hashiguchi
(K)
Barry Heller
(B)
Luis Berthin Hernández Hernández
(LB)
Joselito Hernández Pichardo
(J)
Elizea Horne
(E)
Jian-Pei Huang
(JP)
Li-Min Huang
(LM)
Sandra Hurtado
(S)
Kazushige Ikeda
(K)
Yasunori Ishihara
(Y)
Naseem Jaffrani
(N)
Oley Jallow
(O)
Robert Jeanfreau
(R)
Xuezhi Jiang
(X)
Isik Johansen
(I)
Peter Johnson
(P)
Lisa Jose
(L)
Beate Kampmann
(B)
Anu Kantele
(A)
Hisham Keblawi
(H)
Joseph Kilianski
(J)
Yoon Ha Kim
(YH)
Satu Kokko
(S)
Kenzo Kosaka
(K)
Leonard Krilov
(L)
Outi Laajalahti
(O)
Laurie Landeen
(L)
Blake Landry
(B)
Joanne Langley
(J)
David Larsen
(D)
Chien-Yu Lin
(CY)
Conrado Llapur
(C)
Johannes Lombaard
(J)
Shabir Madhi
(S)
Christ-Ann Magloire
(CA)
Yvonne Maldonado
(Y)
Darvy Mann
(D)
Helen Marshall
(H)
Federico Martinón-Torres
(F)
Paul Matherne
(P)
Bassem Maximos
(B)
Kristin McDay
(K)
David Metz
(D)
Torri Metz
(T)
Hugh Miller
(H)
Jane Miller
(J)
Vicki Miller
(V)
Mariano Miranda Valdivieso
(M)
Emilio Monteagudo Montesinos
(E)
Gregory Moore
(G)
Franklin Morgan
(F)
Tomoko Moritani
(T)
Mirella Mourad
(M)
Paulo Nader
(P)
Albert Nassir
(A)
Silvina Natalini Martinez
(S)
Luis Navarro
(L)
Aftab Naz
(A)
Jason Newland
(J)
Jose Novoa Pizarro
(J)
Mora Obed
(M)
Min-Jeong Oh
(MJ)
Claire Oluwalana
(C)
Richard Ondrizek
(R)
Perry Osborn
(P)
Tolulope Osowo
(T)
Takeo Otsuki
(T)
Enrique Oyarzún Ebensperger
(E)
Pauliina Paavola
(P)
Kristy Palomares
(K)
Joong Park
(J)
Esther Park-Hwang
(E)
Rekha Patel
(R)
Dawnette Peppler
(D)
Gonzalo Pérez Marc
(G)
Roxanne Pero
(R)
Nicole Perreras
(N)
Charles Plimpton
(C)
Raymond Poliakin
(R)
Stephen Pound
(S)
Heather Pugmire
(H)
Edwin Ramirez
(E)
Alan Rappleye
(A)
Michael Rausch
(M)
Peter Richmond
(P)
Kyle Rickner
(K)
Cynthia Robbins
(C)
John Roberts
(J)
Darrell Robinson
(D)
Charles Rogers
(C)
Pablo Rojo Conejo
(P)
Tracy Roth
(T)
Henry Rozycki
(H)
Antonio Saad
(A)
Tetsuhiro Sakihara
(T)
Abril Salinas Quero
(A)
Megan Schellinger
(M)
Elizabeth Schlaudecker
(E)
Michael Scutella
(M)
Koji Seo
(K)
Hyun-Joo Seol
(HJ)
Ilkka Seppä
(I)
Charles Sharp
(C)
John Sherman
(J)
Heidi Siebert
(H)
Eric Simoes
(E)
Daniel Skupski
(D)
Jane Sneed
(J)
Adriana Soto
(A)
Gary Soucie
(G)
Nina Staerke
(N)
Stephen Stamatis
(S)
Thorsten Stanley
(T)
Renato T Stein
(RT)
Scott Striplin
(S)
Stephen Stripling
(S)
Jack Swanson
(J)
Nao Taguchi
(N)
Bruce Tapiero
(B)
John Thorp
(J)
Juan Carlos Tinoco Favila
(JC)
Alan Tita
(A)
Van Tran
(V)
Marie-Louise Vachon
(ML)
Marlies van Houten
(M)
Sergio L Vargas
(SL)
Tiago Veras
(T)
Timothy Villegas
(T)
Keith Vrbicky
(K)
Stuart Weprin
(S)
John Wideman
(J)
Hugh Wilkinson
(H)
Frank Williams
(F)
Karen Wilson
(K)
Lori Wittman
(L)
Samuel Wolf
(S)
Hiroshi Yamashita
(H)
Inci Yildirim
(I)
Ali Zakir
(A)
Heather Zar
(H)
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