Seasonal quadrivalent mRNA vaccine prevents and mitigates influenza infection

TLDR

Seasonal influenza causes millions of infections and hundreds of thousands of deaths annually, but vaccine efficacy varies yearly due to antigenic drift of hemagglutinin and egg‑based manufacturing, prompting exploration of alternative platforms such as mRNA. This study investigates the immunogenicity and protective efficacy of a quadrivalent mRNA vaccine encoding hemagglutinin from four contemporary influenza strains. The authors immunized mice with a 120 μg total dose of the quadrivalent mRNA vaccine and evaluated antibody responses and protection after challenge with A/California/04/2009. The vaccine induced robust, strain‑specific antibody titers and conferred complete protection against morbidity and mortality even at 1 μg per antigen, with a single 10 μg dose preventing weight loss, supporting its promise for influenza prevention and mitigation.

Abstract

Abstract Annually, seasonal influenza is responsible for millions of infections and hundreds of thousands of deaths. The current method for managing influenza is vaccination using a standardized amount of the influenza virus’ primary surface antigen, hemagglutinin (HA), as the intended target of the immune response. This vaccination strategy results in vaccines with variable efficacy year to year due to antigenic drift of HA, which can be further exacerbated by manufacturing processes optimizing growth of vaccine virus in eggs. Due to these limitations, alternative vaccine platforms are actively being explored to improve influenza vaccine efficacy, including cell-based, recombinant protein, and mRNA vaccines. mRNA’s rapid, in vitro production makes it an appealing platform for influenza vaccination, and the success of SARS-CoV-2 mRNA vaccines in the clinic has encouraged the development of mRNA vaccines for other pathogens. Here, the immunogenicity and protective efficacy of a quadrivalent mRNA vaccine encoding HA from four seasonal influenza viruses, A/California/07/2009 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008 (B-Victoria lineage), and B/Phuket/3073/2013 (B-Yamagata lineage), was evaluated. In mice, a 120 μg total dose of this quadrivalent mRNA vaccine induced robust antibody titers against each subtype that were commensurate with titers when each antigen was administered alone. Following A/California/04/2009 challenge, mice were fully protected from morbidity and mortality, even at doses as low as 1 μg of each antigen. Additionally, a single administration of 10 μg of quadrivalent mRNA was sufficient to prevent weight loss caused by A/California/04/2009. These results support the promise of this mRNA vaccine for prevention and mitigation of influenza vaccine.