Safety, Tolerability, and Immunogenicity of Revaccination With mRNA-1345 RSV Vaccine Administered 24 Months Following a Primary Dose in Adults ≥60 Years of Age.

Abstract

mRNA-1345 is a respiratory syncytial virus (RSV) vaccine approved for prevention of RSV-associated lower respiratory tract disease in individuals aged ≥60 years and those aged 18-59 years at high-risk of severe RSV disease. Protection offered by a single dose of an RSV vaccine is not expected to be lifelong, and data on revaccination are needed. This randomized, observer-blind, placebo-controlled, phase 3 study evaluated mRNA-1345 (50µg) revaccination approximately 24 months after primary vaccination in adults ≥60 years. Participants were randomized 2:1 to receive mRNA-1345 as a revaccination dose or placebo. Primary objectives were to assess safety and to demonstrate noninferiority of RSV-A and RSV-B neutralizing antibody (nAb) responses following revaccination compared with the primary dose. Overall, 1,502 participants received an injection at 24 months post-primary dose (mRNA-1345, n=998; placebo, n=504). mRNA-1345 revaccination was generally well tolerated, with injection site pain, fatigue, myalgia, headache, arthralgia, and chills the most frequently reported, solicited adverse reactions. No safety concerns were identified. Noninferiority was demonstrated for the co-primary endpoints (RSV-A and RSV-B nAb responses) based on a pre-specified noninferiority margin of 1.5; the lower bound of 95% CI for the geometric mean titer ratio (post-revaccination titer vs day 29 post-primary vaccination) was greater than 1/1.5 (approximately 0.667). mRNA-1345 revaccination at 24 months was well-tolerated and elicited nAb responses non-inferior to primary vaccination. Based on nAb titers comparable to those after primary vaccination, mRNA-1345 revaccination has the potential to provide extended protection against RSV disease once timing for revaccination is determined. Clinical Trials Registration. NCT05127434 (https://clinicaltrials.gov/study/NCT05127434).