An mRNA-based seasonal influenza vaccine in adults: Results of two phase 3 randomized clinical trials and correlate of protection analysis of hemagglutination inhibition titers

The safety, immunogenicity, and efficacy of the original formulation of the investigational mRNA-1010 vaccine for seasonal influenza were investigated in two randomized, active-controlled, phase 3 trials in adults (NCT05415462 and NCT05566639), and the results were used to evaluate hemagglutination inhibition (HAI) titers as correlates of risk and protection against influenza-like illness. mRNA-1010 (50-µg) demonstrated an acceptable reactogenicity and safety profile among the >14,000 adult participants vaccinated in both trials. The efficacy profile of mRNA-1010 was generally reflective of immunogenicity findings, with higher immune responses against influenza A strains and lower responses against influenza B strains relative to an active comparator (licensed inactivated influenza vaccine). An analysis of HAI titers as a correlate of protection against influenza infection provided support for its use as a surrogate endpoint for mRNA-1010, similar to licensed influenza vaccines. These findings support further optimization and development of mRNA-1010 against seasonal influenza.