Safety, Tolerability, and Immunogenicity of mRNA-1345 in Adults at Increased Risk for RSV Disease Aged 18 to 59 Years.

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 and RSV-B neutralizing antibody (nAb) geometric mean titers (GMTs) for the 50-μg dose compared to 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: 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. Injection-site pain, fatigue, headache, and myalgia were the most common ARs. Day 29 nAb GMTs in the 50-µg group met noninferiority criteria: RSV-A GMT ratio (GMR) was 1.2 (95% CI: 1.1-1.3); RSV-B GMR was 1.1 (95% CI: 1.0-1.2). Noninferiority was also demonstrated for seroresponse rate differences: RSV-A at 11.8% (95% CI: 7.8-15.5); RSV-B at 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. Background: NCT06067230.