Efficacy and Safety of an Ad26.RSV.preF–RSV preF Protein Vaccine in Older Adults

This phase 2b, randomized, double-blind, placebo-controlled trial (CYPRESS) evaluated the efficacy, immunogenicity, and safety of a single-dose Ad26.RSV.preF-RSV preF protein vaccine in adults aged 65 and older. Conducted across 40 U.S. centers, the study enrolled 5782 participants and assessed RSV-mediated lower respiratory tract disease using three symptom-based case definitions. Vaccine efficacy was 80.0%, 75.0%, and 69.8% for definitions 1, 2, and 3, respectively. The vaccine boosted RSV A and B neutralizing antibodies and preF IgG levels, and induced robust RSV-F-specific T-cell responses. Adverse events were more frequent in the vaccine group but mostly mild-to-moderate; serious events and fatalities were comparable across groups. The vaccine showed consistent efficacy across age and risk subgroups, with promising immunogenicity and safety outcomes.

This phase 2b, randomized, double-blind, placebo-controlled trial (CYPRESS) evaluated the efficacy, immunogenicity, and safety of a single-dose Ad26.RSV.preF-RSV preF protein vaccine in adults aged 65 and older. Conducted across 40 U.S. centers, the study enrolled 5782 participants and assessed RSV-mediated lower respiratory tract disease using three symptom-based case definitions. Vaccine efficacy was 80.0%, 75.0%, and 69.8% for definitions 1, 2, and 3, respectively. The vaccine boosted RSV A and B neutralizing antibodies and preF IgG levels, and induced robust RSV-F-specific T-cell responses. Adverse events were more frequent in the vaccine group but mostly mild-to-moderate; serious events and fatalities were comparable across groups. The vaccine showed consistent efficacy across age and risk subgroups, with promising immunogenicity and safety outcomes.