4.8 Article

Assessment of a quadrivalent nucleoside-modified mRNA vaccine that protects against group 2 influenza viruses

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.2206333119

Keywords

influenza virus; mRNA vaccine; nucleoside modification; lipid nanoparticle; T cells

Funding

  1. NIH [R01-AI146101]
  2. Collaborative Influenza Vaccine Innovation Centers (CIVICs) contract [75N93019C00051]
  3. Biotechnological National Laboratory, Szeged, Hungary
  4. Rosztoczy Foundation

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This study demonstrates the use of nucleoside-modified mRNA-LNP vaccines to target multiple influenza virus antigens. The results show that the vaccine induces antigen-specific immune responses and provides effective protection against various influenza viruses in mice.
Combined vaccine formulations targeting not only hemagglutinin but also other influenza virus antigens could form the basis for a universal influenza virus vaccine that has the potential to elicit long-lasting, broadly cross-reactive immune responses. Lipid nanoparticle (LNP)-encapsulated messenger RNA (mRNA) vaccines can be utilized to efficiently target multiple antigens with a single vaccine. Here, we assessed the immunogenicity and protective efficacy of nucleoside-modified mRNA-LNP vaccines that contain four influenza A group 2 virus antigens (hemagglutinin stalk, neuraminidase, matrix protein 2, and nucleoprotein) in mice. We found that all vaccine components induced antigen-specific cellular and humoral immune responses after administration of a single dose. While the monovalent formulations were not exclusively protective, the combined quadrivalent formulation protected mice from all challenge viruses, including a relevant H1N1 influenza virus group 1 strain, with minimal weight loss. Importantly, the combined vaccine protected from morbidity at a dose of 125 ng per antigen after a single vaccination in mice. With these findings, we confidently conclude that the nucleoside-modified mRNA-LNP platform can be used to elicit protection against a large panel of influenza viruses.

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