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

Abstract

BACKGROUNDWhether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)-associated lower respiratory tract illness in newborns and infants is uncertain. METHODSIn 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 proteinbased (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. RESULTSAt 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). CONCLUSIONSRSVpreF 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.

Maternal RSV vaccine: Further analysis is urged on preterm births

“…In a prespecified interim analysis of Pfizer’s related phase 3 trial published in April, 201 babies (5.6%) were born prematurely to vaccinated mothers v 169 babies (4.7%) in the placebo group 12. According to the protocol of the trial, Pfizer was studying preterm birth as an “adverse event of special interest.”12…”

Rational design of a highly immunogenic prefusion-stabilized F glycoprotein antigen for a respiratory syncytial virus vaccine

“…RSVpreF has demonstrated efficacy against symptomatic RSV infection in a human challenge study (39), and it has been advanced to global, pivotal phase 3 efficacy trials in pregnant women and their infants (NCT04424316) and older adults (NCT05035212) (40). Both studies met their primary efficacy endpoint, confirming the ability of RSVpreF to protect young infants by maternal immunization and older adults by active immunization (41,42).…”

Preventing respiratory syncytial virus bronchiolitis in infants

“…Maternal vaccination strategies have recently shown great progress in phase 3 trials. Pfizer recently reported a preplanned, interim analysis showing that maternal vaccination with its prefusion protein vaccine was 81.8% effective (95% CI 40.6% to 96.3%) at preventing severe RSV infection through the first 90 days of the infant’s life 10. However, GSK’s trial of another prefusion protein maternal vaccine halted recruitment early because of concerns about an increased incidence of preterm delivery among vaccinated participants 1112.…”