Immunogenicity, reactogenicity, and safety of an mRNA-based seasonal influenza and SARS-CoV-2 multicomponent vaccine, mRNA-1083, in adults aged ≥50 years in Japan.
A multicomponent vaccine targeting seasonal influenza and coronavirus disease 2019 (COVID-19) may reduce disease burden by providing simultaneous protection in a single injection. We report findings from Part 1 (Japan) of a phase 3, Asia-Pacific, randomized, observer-blind study evaluating immunogenicity, reactogenicity, and safety of mRNA-based multicomponent vaccine mRNA-1083, combining influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens. Participants aged ≥50 years were randomized (1:1) to receive mRNA-1083 + placebo or Japan-licensed influenza hemagglutinin (HA) vaccine + mRNA-1273. Overall, 2022 participants were randomized, and 2013 received study intervention. At Day 29, mRNA-1083 elicited noninferior immune responses versus active comparators for all evaluated influenza strains and SARS-CoV-2. Among high-risk participants (aged ≥65 years and 60 to <65 years with ≥1 comorbidity), noninferiority of mRNA-1083 was demonstrated for comparator-matched influenza strains and SARS-CoV-2. In the overall study population, mRNA-1083 demonstrated superiority for the comparator-matched influenza strains and for SARS-CoV-2. At Day 181, immune responses remained above baseline and were comparable to or numerically higher than those elicited by active comparators. Most solicited adverse reactions were grade 1 or 2. There were no cases of myocarditis or pericarditis, and no reported serious adverse events or deaths related to study intervention. Overall, mRNA-1083 demonstrated an acceptable safety profile, eliciting noninferior and superior immune responses against influenza and SARS-CoV-2 in the high-risk and overall study population, respectively. Immune responses were maintained through 6 months post-vaccination. These findings support mRNA-1083 as a single-dose approach to seasonal vaccination against influenza and SARS-CoV-2 in adults ≥50 years. ClinicalTrials.govidentifier: NCT06694389 (https://clinicaltrials.gov/study/NCT06694389).