Bivalent RSV Prefusion F Vaccine to Prevent Hospitalizations in Adults

BACKGROUND: Respiratory syncytial virus (RSV) is an important cause of severe respiratory disease in adults, with the highest burden among older adults and individuals with chronic health conditions. The bivalent RSV prefusion F (RSVpreF) vaccine has been shown to prevent RSV-associated respiratory illness, but data from randomized trials regarding its effect on hospitalization outcomes are limited. METHODS: In this pragmatic, individually randomized, open-label trial conducted in Denmark and Spain, adults were assigned in a 1:1 ratio to receive RSVpreF or no vaccine. During the first year of enrollment, participants who were 60 years of age or older in Denmark were enrolled; during the second year, eligibility was expanded to participants 18 years of age or older in Denmark and Spain. The results of the first year of enrollment have been reported previously; because fewer RSV-related hospitalization events than anticipated occurred in the first year, demographic and geographic enrollment was expanded. The primary endpoint was RSV-related respiratory tract disease (RTD) hospitalization in the intention-to-treat population. Secondary endpoints included RSV-related lower RTD and all-cause RTD hospitalization. RESULTS: Of 513,358 participants who underwent random assignment during the 2024-2025 and 2025-2026 winter seasons, the incidence rate of RSV-related RTD hospitalization was 0.16 events per 1000 person-years in the RSVpreF group and 0.55 events per 1000 person-years in the control group, corresponding to an estimated vaccine effectiveness of 70.3% (95% confidence interval [CI], 49.7-83.2). The incidence of RSV-related lower RTD hospitalization was 0.11 and 0.39 events per 1000 person-years in the RSVpreF vaccine and no-vaccine groups, respectively, corresponding to an estimated vaccine effectiveness of 71.1% (95% CI, 45.4-85.7) and the incidence of all-cause RTD hospitalization was 11.16 and 12.01 events per 1000 person-years in the RSVpreF vaccine and no-vaccine groups, respectively, corresponding to an estimated vaccine effectiveness of 7.1% (95% CI, -0.3-13.9). The incidence of serious adverse events was 2.0% in the RSVpreF vaccine group and 2.2% in the no-vaccine group. CONCLUSIONS: In a randomized trial that included expanded demographic and geographic enrollment during a second RSV season, the RSVpreF vaccine was associated with a lower incidence of RSV-related respiratory tract disease hospitalization as compared to no vaccine. (Funded by Pfizer; ClinicalTrials.gov number, NCT06684743.).