Efficacy, Immunogenicity, and Safety of the Bivalent Respiratory Syncytial Virus (RSV) Prefusion F Vaccine in Older Adults Over 2 RSV Seasons

BACKGROUND: Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract illness (LRTI) in older adults. RSV prefusion F (RSVpreF) is a bivalent stabilized prefusion F vaccine containing RSV-A and RSV-B antigens. In this phase 3 trial in persons aged ≥60 years, RSVpreF demonstrated vaccine efficacy (VE) of 88.9% and 77.8% against RSV-associated LRTI with ≥3 symptoms at the end of RSV seasons 1 and 2, respectively. We describe final safety and efficacy results and present immunogenicity data. METHODS: This study was conducted over 2 RSV seasons. Participants were randomized (1:1) to RSVpreF 120-µg or placebo. A secondary objective was to describe RSVpreF immunogenicity 1 month post-vaccination and before season 2 visits in participants from the United States and Japan. RESULTS: One-month post-vaccination neutralization titer geometric mean fold rise (GMFR) was 12.1 for combined RSV-A/RSV-B. Geometric mean titers decreased at the preseason 2 visit but remained substantially higher than baseline (RSV-A/RSV-B GMFR = 4.7). One month post-vaccination, GMFRs for RSV-A/RSV-B neutralizing responses were 12.0 to 13.0 for subgroups stratified by age (60-69, 70-79, ≥80 years). RSV-A/RSV-B GMFRs in participants with prespecified chronic conditions were generally similar to those without (range, 11.4-14.4). A consistent favorable safety profile and durable VE were seen through 2 RSV seasons. CONCLUSIONS: High RSV neutralizing titers were observed 1 month after RSVpreF vaccination in persons aged ≥60 years, with similarly robust responses across subgroups. These immune responses corresponded with high RSVpreF VE against RSV-associated LRTI. RSVpreF had a favorable safety profile over 2 seasons. Clinical Trials Registration. NCT05035212; EudraCT, 2021-003693-31.