Safety and immunogenicity of an mRNA-based RSV vaccine in Japanese older adults aged ≥ 60 years: A phase 1, randomized, observer-blind, placebo-controlled trial

Background: Respiratory syncytial virus (RSV) represents a global health concern, including in older adults. This study assessed the safety and immunogenicity of mRNA-1345, an investigational mRNA RSV vaccine, in adults aged >= 60 years of Japanese descent. Methods: In this phase 1, randomized, observer-blind, placebo-controlled study, participants were randomized to receive one injection of mRNA-1345 100 mu g or placebo. Solicited local and systemic adverse reactions (ARs) were collected within 7 days following injection. Unsolicited adverse events (AEs) were collected up to 28 days after injection; AEs of special interest, medically attended AEs, and serious AEs were collected through end of study. Immunogenicity was assessed at baseline and months 1, 2, 3, and 6 following injection. Results: Twenty-five adults of Japanese descent aged >= 60 years received one injection of mRNA-1345 100 mu g (n = 21) or placebo (n = 4). mRNA-1345 was well-tolerated; the most common local and systemic solicited ARs were injection site pain, and fatigue and myalgia, respectively, which were generally mild to moderate and transient. No serious AEs were reported. Neutralizing (nAb) and binding (bAb) antibodies were detectable at baseline, consistent with prior RSV exposure. mRNA-1345 boosted RSV nAb titers and preF bAb concentrations 1 month post-injection (geometric mean fold rise: RSV-A nAb, 11.2; RSV-B nAb, 6.6; preF bAb, 9.1). Titers among mRNA-1345 recipients remained above baseline through 6 months. Conclusions: mRNA-1345 100 mu g was well-tolerated among older adults of Japanese descent and induced nAbs and bAbs which were durable through 6 months, supporting its continued development.