Abstract
BACKGROUND: Older individuals and adults with certain chronic or immunocompromising health conditions are at increased risk of severe respiratory syncytial virus (RSV) disease. METHODS: In this phase 3 randomized trial of RSVpreF safety and immunogenicity in 18-59-year-olds at high risk of severe RSV disease, participants were randomized 2:1 to 1 RSVpreF (120 µg) or placebo dose. Primary safety endpoints included reactogenicity events and adverse events (AEs) through 7 days and 1 month after vaccination, respectively, and serious AEs (SAEs) and newly diagnosed chronic medical conditions (NDCMCs) throughout the study. In primary analyses, immunogenicity elicited 1 month after RSVpreF was bridged to a randomly selected subset of ≥60-year-olds receiving RSVpreF from the immunogenicity subset in the pivotal phase 3 RENOIR trial, which demonstrated RSVpreF efficacy. Noninferiority was declared if 95% confidence interval (CI) lower bounds were >.667 (neutralizing titer adjusted geometric mean ratios) and >-10% (seroresponse rate differences) for RSV-A and RSV-B. RESULTS: Overall, 678 participants received RSVpreF (n = 453) or placebo (n = 225). Most reactogenicity events were mild/moderate; severe events occurred in ≤2.0% of participants overall. AE frequencies were similar in RSVpreF (7.1%) and placebo recipients (7.6%). No vaccine-related SAEs or NDCMCs were reported. One month after RSVpreF administration, noninferiority criteria were met in 18-59-year-olds versus ≥60-year-olds for RSV-A and RSV-B neutralizing titers and seroresponse rates. CONCLUSIONS: RSVpreF was well tolerated with no safety concerns and demonstrated immunobridging to efficacy in 18-59-year-olds at high risk of severe RSV disease versus ≥60-year-olds in whom efficacy was previously demonstrated, supporting use of RSVpreF to prevent RSV-associated disease in this population. NCT05842967.