Background

Seasonal influenza, which occurs annually, is a major respiratory infectious disease that causes numerous hospitalizations and deaths. In particular, influenza A and B viruses are major causes of severe illness. In the past, vaccines have mainly used embryonated eggs or cell culture methods. However, these traditional platforms have limitations in that they cannot quickly respond to viral mutations and their preventive effects rapidly decrease. As a result, the messenger ribonucleic acid (mRNA) platform is emerging as a promising alternative. mRNA vaccines have the advantage of being able to quickly change the design because they directly deliver the viral antigen genetic information. In addition, it has the flexibility to induce strong immunogenicity even without immunostimulants, which are essential for inducing immune responses. In particular, the embryonated egg culture method has the risk of 'egg-adapted mutation', in which the virus itself undergoes a mutation during the production process. This has been pointed out as a major cause of reduced vaccine efficacy by causing a mismatch with the actual circulating influenza virus.

Key Findings

U.S. researchers conducted a phase 2 clinical trial to evaluate the safety and immunogenicity of 'mRNA-1010', a candidate mRNA-based seasonal influenza vaccine, in a randomized manner in 270 healthy adults aged 18-49 years. The clinical trial (NCT05868382) was conducted from May to December 2023. Participants received a single dose of one of three mRNA-1010 formulations designed to express the hemagglutinin (HA) protein of the influenza virus strains recommended by the World Health Organization (WHO) at different dose levels. As a result of the researchers tracking adverse reactions and immune responses after vaccination, all mRNA-1010 formulations showed excellent tolerability. No clinically significant safety issues were identified. In the entire vaccinated group, HA-specific humoral and cellular immune responses were successfully induced against all influenza virus strains evaluated. Notably, a significantly higher immune response was elicited against influenza B viruses. The researchers stated that the optimized new formulation induced stronger antibody formation ability, especially against influenza B strains, which are known to be difficult to induce immunity, compared to the existing first-generation mRNA-1010 formulation. This is due to the difference in the design that precisely adjusts the antigen expression rate.

Significance and Prospects

This study is significant in that it demonstrates that influenza vaccines using the mRNA platform can overcome the insufficient defense of traditional vaccines. In particular, the optimized formulation has demonstrated excellent immunogenicity in the influenza B virus strain, which has been known to be difficult to induce immunity, increasing the possibility of commercialization of the next-generation influenza vaccine. This provides a clue to solve the frequent mismatch problem of existing influenza vaccines. However, further research is needed before it reaches the commercialization stage. Since this phase 2 clinical trial was conducted only on relatively young and healthy adults, the efficacy and safety in high-risk groups for influenza, such as the elderly and children, have not yet been fully verified. A phase 3 clinical trial to confirm the prevention rate in a large number of vaccinated subjects and an evaluation of the long-term persistence of the immune response will be key tasks in the future. In addition, the industry must work together to address the logistical challenges of quickly updating and distributing vaccines in time for the upcoming fall influenza season.