Phase 1/2 randomized, observer-blind clinical trial of a first-generation, mRNA-based vaccine against seasonal influenza and COVID-19 in healthy adults

A multicomponent vaccine against seasonal influenza and COVID-19 could reduce disease burden in adults by providing simultaneous protection in a single-dose regimen. The first-generation, mRNA-based, multicomponent mRNA-1073 vaccine, combining antigens encoded by mRNA-1010 (influenza) and mRNA-1273 (COVID-19) vaccines, was investigated in a phase 1/2 clinical trial. This stratified, observer-blinded study randomly assigned healthy adults (18-75 years) to receive mRNA-1073 (25-µg, 50-µg, or 100-µg) + placebo, mRNA-1273 (50-μg) + placebo, mRNA-1010 (50-μg) + placebo, or co-administered mRNA-1010 (50-μg) + mRNA-1273 (50-μg) on day 1. Primary study objectives were safety and reactogenicity. Secondary study objectives assessed humoral immunogenicity against vaccine-matched influenza and SARS-CoV-2 strains at day 29 and all evaluable time points through day 181. An exploratory objective was to further characterize immune responses across the study vaccines. Overall, 550 participants were randomly assigned to receive study vaccination. mRNA-1073 exhibited dose-dependent reactogenicity. Most solicited adverse reactions were grade 1 or 2 in severity; no grade 4 events, serious adverse events related to study vaccination, or deaths were reported. A single dose of mRNA-1073 elicited durable immune responses through 6 months against all vaccine-matched influenza and SARS-CoV-2 strains. Systems serology analysis indicated that mRNA-1073 induced robust, balanced antibody responses with comparable immune profiles to mRNA-1010 + mRNA-1273. mRNA-1073 had an acceptable safety profile and elicited durable immune responses against all vaccine-matched influenza and SARS-CoV-2 strains, supporting ongoing evaluations of mRNA-based multicomponent vaccines that simultaneously protect against seasonal influenza and COVID-19 in a single dose.<b>Registration</b>: ClinicalTrials.gov identifier: NCT05375838 (https://clinicaltrials.gov/study/NCT05375838).