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Development of a pentavalent broadly protective nucleoside-modified mRNA vaccine against influenza B viruses

Author

Listed:
  • Norbert Pardi

    (University of Pennsylvania)

  • Juan Manuel Carreño

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • George O’Dell

    (Icahn School of Medicine at Mount Sinai)

  • Jessica Tan

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Csaba Bajusz

    (University of Pennsylvania
    Institute of Genetics, Biological Research Centre)

  • Hiromi Muramatsu

    (University of Pennsylvania)

  • Willemijn Rijnink

    (Icahn School of Medicine at Mount Sinai)

  • Shirin Strohmeier

    (Icahn School of Medicine at Mount Sinai)

  • Madhumathi Loganathan

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Dominika Bielak

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Molly M. H. Sung

    (Acuitas Therapeutics)

  • Ying K. Tam

    (Acuitas Therapeutics)

  • Florian Krammer

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Meagan McMahon

    (Icahn School of Medicine at Mount Sinai)

Abstract

Messenger RNA (mRNA) vaccines represent a new, effective vaccine platform with high capacity for rapid development. Generation of a universal influenza virus vaccine with the potential to elicit long-lasting, broadly cross-reactive immune responses is a necessity for reducing influenza-associated morbidity and mortality. Here we focus on the development of a universal influenza B virus vaccine based on the lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) platform. We evaluate vaccine candidates based on different target antigens that afford protection against challenge with ancestral and recent influenza B viruses from both antigenic lineages. A pentavalent vaccine combining all tested antigens protects mice from morbidity at a very low dose of 50 ng per antigen after a single vaccination. These findings support the further advancement of nucleoside-modified mRNA-LNPs expressing multiple conserved antigens as universal influenza virus vaccine candidates.

Suggested Citation

  • Norbert Pardi & Juan Manuel Carreño & George O’Dell & Jessica Tan & Csaba Bajusz & Hiromi Muramatsu & Willemijn Rijnink & Shirin Strohmeier & Madhumathi Loganathan & Dominika Bielak & Molly M. H. Sung, 2022. "Development of a pentavalent broadly protective nucleoside-modified mRNA vaccine against influenza B viruses," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32149-8
    DOI: 10.1038/s41467-022-32149-8
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    Cited by:

    1. Tejas Menon & Patricia T. Illing & Priyanka Chaurasia & Hayley A. McQuilten & Chloe Shepherd & Louise C. Rowntree & Jan Petersen & Dene R. Littler & Grace Khuu & Ziyi Huang & Lilith F. Allen & Steve R, 2024. "CD8+ T-cell responses towards conserved influenza B virus epitopes across anatomical sites and age," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    2. Rebecca A. Leonard & Kaitlyn N. Burke & Rachel L. Spreng & Andrew N. Macintyre & Ying Tam & Mohamad-Gabriel Alameh & Drew Weissman & Nicholas S. Heaton, 2024. "Improved influenza vaccine responses after expression of multiple viral glycoproteins from a single mRNA," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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