Efficacy, Immunogenicity, and Safety of an Investigational Maternal Respiratory Syncytial Virus Prefusion F Protein-Based Vaccine

Abstract

Background In this phase 3 trial of an investigational maternal respiratory syncytial virus prefusion F protein-based vaccine (RSVPreF3-Mat), a higher rate of preterm birth was observed in the vaccine (6.8%) versus the placebo group (4.9%). Trial enrollment and vaccination were stopped. Results of investigations into this safety signal were reported previously. Here, we describe end-of-Trial efficacy, immunogenicity, and safety results. Methods Women 18-49 years old were randomized 2:1 to receive 1 dose of RSVPreF3-Mat (n = 3557) or placebo (n = 1771) at 240/7-340/7 weeks' gestation. Primary outcomes were any and severe medically assessed RSV-Associated lower respiratory tract disease (MA-RSV-LRTD) in infants until 6 months postbirth and safety until 12 months postbirth. Other efficacy outcomes were evaluated, along with immunogenicity (until 6 months postpartum/birth) and safety in mothers and infants. Results Efficacy (with 95% credible interval) in infants until 6 months postbirth was 65.5% (37.5%-82.0%) against any MA-RSV-LRTD, 69.0% (33.0%-87.6%) against severe MA-RSV-LRTD, and 50.1% (-3.6% to 75.8%) against RSV hospitalization; it waned over time thereafter. Efficacy against MA-RSV-LRTD was 47.8% (-25.8% to 77.3%) in low-and middle-income and 75.9% (46.1%-91.5%) in high-income countries. RSVPreF3-Mat induced a substantial increase in RSV-A neutralization titers in mothers, with efficient transplacental transfer of antibodies that persisted in infants until at least 6 months postbirth. Conclusions Consistent with the high titers of transplacentally transferred antibodies, this trial suggests a reduced risk of any/severe MA-RSV-LRTD and RSV hospitalization until 6 months postbirth in infants born to mothers immunized with RSVPreF3-Mat during pregnancy. However, vaccine development was terminated due to an identified preterm birth risk. Clinical Trials Registration. NCT04605159.