2025/06/04 by Erick F. Mayer, Ann R. Falsey, Rebecca A. Clark +18 · 1 voice
Agricultural and Biological Sciences · Biochemistry, Genetics and Molecular Biology · Medicine · #Animal Virus Infections Studies #Respiratory viral infections research #Virus-based gene therapy research
paper · pdf · doi:10.1093/cid/ciaf292
openalex publication_date 2025/06/04 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30
BACKGROUND: Respiratory syncytial virus (RSV) is a significant health risk for adults aged 18-59 years with chronic medical conditions. METHODS: This ongoing, randomized, double-blind phase 3 trial evaluates safety and immunogenicity of the RSV vaccine, mRNA-1345, in adults aged 18-59 years at increased risk for RSV-associated lower respiratory tract disease (LRTD). Participants received a single 50-µg (licensed dose) or 30-µg dose. Co-primary immunogenicity objectives were to demonstrate noninferiority of day 29 RSV-A/B neutralizing antibody (nAb) geometric mean titers (GMTs) for the 50-μg dose compared with those observed in adults aged ≥60 years from the phase 3 pivotal efficacy trial. The other primary objective was to evaluate safety and tolerability. RESULTS: A total of 999 participants received mRNA-1345 (50 µg, n = 502; 30 µg, n = 497). Most solicited adverse reactions (ARs) were mild to moderate with a median duration of 2 days. Day 29 nAb GMTs in the 50-µg group met noninferiority criteria: RSV-A GMT ratio (GMR), 1.2 (95% confidence interval [CI], 1.1-1.3); RSV-B GMR, 1.1 (95% CI, 1.0-1.2). Noninferiority was also demonstrated for seroresponse rate differences: RSV-A, 11.8% (95% CI, 7.8-15.5); RSV-B, 10.8% (95% CI, 5.9-15.6). Immune responses were consistent across subgroups and remained above baseline through day 181. CONCLUSIONS: In adults aged 18-59 years at increased risk for RSV-LRTD, a 50-µg dose of mRNA-1345 was well tolerated and elicited RSV-A and RSV-B nAb responses noninferior to those observed in older adults in the pivotal study, supporting inference of efficacy in this population. CLINICAL TRIALS REGISTRATION: NCT06067230.