2637. Third Trimester Immunization with an Respiratory Syncytial Virus F Protein Vaccine for the Prevention of RSV Lower Respiratory Tract Infection in Infants

Abstract

Background: Respiratory syncytial virus (RSV) is the leading viral cause of severe lower respiratory tract infection (LRTI) in infants worldwide, with severe disease occurring in the first months of life. We assessed the efficacy of maternal immunization with an RSV F protein vaccine against RSV LRTI over the first 180 days of life. Methods: We enrolled 4,636 women with low‐risk third trimester singleton pregnancies in 11 countries to receive RSV F vaccine or placebo in a randomized, observer‐ blind trial. Women were followed for 6 months post‐delivery, and infants for ∼1 year. Surveillance for RSV LRTI in infants, identified by RT‐PCR detection of RSV, physical examination, and pulse oximetry, was carried out for 180 days from delivery. Results: The RSV F vaccine induced modest reactogenicity and no excess fever. Live births resulted from 98.7% of pregnancies, with no difference between treatment groups in prematurity (< 37 weeks) or mean interval from treatment to delivery. There were no apparent negative impacts on pregnancy, delivery, or infant well‐being. Vaccine immunogenicity resembled that in non‐pregnant women. Transplacental transfer of vaccine‐induced antibodies was markedly more efficient when the interval from immunization to delivery was ≥30 days. 85 to 95% of primary and secondary endpoint RSV LRTI events in the placebo group occurred in the first 90 days of life (see Figure 1). Overall, through 180 days of infant life, RSV was associated with 11.3% of all acute respiratory illnesses and 16.7% of all LRTI, but 49.1% of LRTI with SpO2 < 95% or tachypnea, and 60.3% of all LRTI with SpO2 < 92% in the placebo group. Vaccine efficacy was greatest in the first 75 days of life but clearly persisted to the primary, per‐protocol analysis at 90 days, and was supported by the ITT analysis, per Table 1. Efficacy against all‐cause LRTI with severe hypoxemia (46.0%) or hospitalization (27.8%) was observed in the per‐protocol population, as well as an apparent impact on the clinical diagnosis of pneumonia through both 180 and 364 days. Conclusion: RSV F vaccine in the third trimester was safe and had clinically‐meaningful impacts on RSV and all‐cause LRTI over the first 6 months of life.