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

Abstract

Background RSV is an important cause of lower respiratory tract illness (LRTI) in older adults. RSVpreF is a bivalent stabilized prefusion F vaccine containing antigens against RSV-A and RSV-B. In this phase 3 trial in ≥60-year-olds, 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. Here 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 1 dose of RSVpreF 120-µg or placebo. A secondary objective was to describe RSVpreF immunogenicity 1-month postvaccination and before season 2 visits in a participant subset from the USA and Japan. Results One-month postvaccination 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 postvaccination, GMFRs for RSV-A/RSV-B neutralizing responses ranged from 12.0−13.0 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 was seen through 2 RSV seasons. Conclusion High RSV neutralizing titers were observed 1 month after RSVpreF vaccination in ≥60-year-olds, with similarly robust responses across age subgroups and baseline chronic conditions. These robust immune responses corresponded with high RSVpreF VE against RSV-associated LRTI. RSVpreF had a favorable safety profile over 2 seasons. NCT05035212; EudraCT, 2021-003693-31