Efficacy, Immunogenicity, and Safety of the Bivalent Respiratory Syncytial Virus (RSV) Prefusion F Vaccine in Older Adults Over 2 RSV Seasons
Edward E. Walsh, Daniel Eiras, John Woodside, Qin Jiang, Michael A. Patton, Gonzalo Pérez Marc, Conrado J. Llapur, Mika Rämet, Yasushi Fukushima, Nazreen Hussen, José F. Cardona, Tarek Mikati, Agnieszka Zareba, Kumar Ilangovan, Maria Maddalena Lino, Elena Kalinina, Kena A. Swanson, Alejandra Gurtman, Iona Munjal
Abstract
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.