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
Boris Kandinov, Mieke Soens, Wenmei Huang, Conrado J. Llapur, David J. Ensz, Brandon Essink, Carlos Fierro, Jignesh Vakil, Alicia Pucci, Jia Guo, Sinead Rudden, Kristi Hall, Bryony Hicks, Kristi Schaefers, Honghong Zhou, Chong Ma, Lingyi Zheng, Andrei Avanesov, Yoonyoung Park, Evelyn Du, Jacqueline Miller, Jintanat Ananworanich, Raffael Nachbagauer
Abstract
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.