Durability of RSV Prefusion F Vaccine Protection across Two RSV Seasons

Respiratory syncytial virus (RSV) is an important cause of hospitalization and death among older adults. Although first-season vaccine effectiveness against RSV-related hospitalization has been demonstrated for the bivalent RSV prefusion F protein-based vaccine (RSVpreF), data regarding the durability of protection beyond a single RSV season are lacking.

In a pragmatic, open-label trial with individual randomization, participants 60 years of age or older were assigned in a 1:1 ratio to receive RSVpreF vaccine or no vaccine during the 2024-2025 winter season. Participants were followed through the 2025-2026 winter season to evaluate protection across two consecutive RSV seasons after a single vaccine dose. The primary endpoint was RSV-related respiratory tract disease (RTD) hospitalization. Secondary endpoints included RSV-related and all-cause lower respiratory tract disease hospitalization, all-cause respiratory hospitalization, all-cause cardiorespiratory hospitalization, and all-cause mortality.

Of 131,379 participants who underwent random assignment, 130,991 were included in the intention-to-treat population during the second season. During the second RSV season, the incidence rate of RSV-related RTD hospitalization was 0.11 events per 1000 person-years in the RSVpreF group and 0.25 events per 1000 person-years in the control group, corresponding to a vaccine effectiveness of 56.2% (95% confidence interval [CI], -12.4% to 84.8%), as compared with 83.3% (95% CI, 42.9%-96.9%) during the first season. Across both seasons, the corresponding incidence rates were 0.11 and 0.37 events per 1000 person-years in the RSVpreF and control groups, respectively, with a vaccine effectiveness of 70.6% (95% CI, 39.1%-87.0%). There was no apparent difference in all-cause respiratory and cardiorespiratory hospitalization outcomes in the second season among those randomly assigned to vaccine or no vaccine in the first season.

Among adults 60 years of age or older, the RSVpreF vaccine was associated with a lower incidence of RSV-related respiratory tract disease during a second RSV season as compared to no vaccine. Vaccine effectiveness estimates appeared to be lower in the second season compared to the first. (Funded by Pfizer; ClinicalTrials.gov number, NCT06684743.).