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

Meagan McMahon, George O’Dell, Jessica Tan, András Sárközy, Máté Vadovics, Juan Manuel Carreño, Eduard Puente-Massaguer, Hiromi Muramatsu, Csaba Bajusz, Willemijn Rijnink, Mitchell Beattie, Ying K. Tam, Ericka Kirkpatrick Roubidoux, Isabel Francisco, Shirin Strohmeier, Masaru Kanekiyo, Barney S. Graham, Florian Krammer, Norbert Pardi

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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.

Original languageEnglish
Article numbere2206333119
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number45
StatePublished - 8 Nov 2022


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


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