Randomized, placebo-controlled phase 3 trial evaluating safety, immunogenicity, and reactogenicity of RSVPreF3-Mat in high-risk pregnant women and their infants.

Respiratory syncytial virus (RSV) causes respiratory illness among infants; maternal vaccination confers passive protection through placental antibody transfer. This phase 3, randomized, placebo-controlled trial evaluated safety, reactogenicity, and immunogenicity of RSV prefusion protein F3 maternal vaccine (RSVPreF3-Mat), administered at 240/7 to 360/7 weeks of gestation to high-risk pregnant women (women with obstetric complications and/or human immunodeficiency virus infection or in pregnant adolescents), and their infants up to 1 year post-birth. Enrollment was stopped and the study unblinded after an increased risk of preterm birth, associated with RSVPreF3 vaccine, was observed in another trial in healthy pregnant women. One hundred and sixty-nine maternal participants received either vaccine or placebo. No serious adverse events in maternal or infant participants were considered vaccine-related. Preterm birth occurred in 18.2% and 19.7% of participants in the vaccine and placebo groups, respectively, with one neonatal death in each group. In the vaccine group, increase in maternal neutralizing antibody titers against RSV subtype A and B was observed at Day 31 post-vaccination and remained high at delivery. Geometric mean ratio of titers at delivery over pre-vaccination for RSV A and B were 8.87- and 8.21-fold, respectively. Similarly, anti-RSVPreF3-Mat immunoglobulin G (IgG) levels showed increase at Day 31 post-vaccination and remained high at delivery (14.12-fold increase over pre-vaccination) with placental transfer ratio of RSVPreF3 IgG-specific antibodies at delivery of 1.33. In this study of high-risk pregnant women, RSVPreF3-Mat demonstrated an acceptable safety profile, induced robust immune responses with successful placental antibody transfer, and showed balanced rates of preterm birth between the groups. Trial registration: EudraCT: 2021-000994-96; NCT: NCT04980391.