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Development of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus

Author

Listed:
  • Colleen Furey

    (University of Pennsylvania)

  • Gabrielle Scher

    (University of Pennsylvania)

  • Naiqing Ye

    (University of Pennsylvania)

  • Lisa Kercher

    (St. Jude Children’s Research Hospital)

  • Jennifer DeBeauchamp

    (St. Jude Children’s Research Hospital)

  • Jeri Carol Crumpton

    (St. Jude Children’s Research Hospital)

  • Trushar Jeevan

    (St. Jude Children’s Research Hospital)

  • Christopher Patton

    (St. Jude Children’s Research Hospital
    University of Tennessee Health Science Center)

  • John Franks

    (St. Jude Children’s Research Hospital)

  • Adam Rubrum

    (St. Jude Children’s Research Hospital)

  • Mohamad-Gabriel Alameh

    (University of Pennsylvania
    University of Pennsylvania)

  • Steven H. Y. Fan

    (Acuitas Therapeutics)

  • Anthony T. Phan

    (University of Pennsylvania)

  • Christopher A. Hunter

    (University of Pennsylvania)

  • Richard J. Webby

    (St. Jude Children’s Research Hospital)

  • Drew Weissman

    (University of Pennsylvania
    University of Pennsylvania)

  • Scott E. Hensley

    (University of Pennsylvania)

Abstract

mRNA lipid nanoparticle (LNP) vaccines would be useful during an influenza virus pandemic since they can be produced rapidly and do not require the generation of egg-adapted vaccine seed stocks. Highly pathogenic avian influenza viruses from H5 clade 2.3.4.4b are circulating at unprecedently high levels in wild and domestic birds and have the potential to adapt to humans. Here, we generate an mRNA lipid nanoparticle (LNP) vaccine encoding the hemagglutinin (HA) glycoprotein from a clade 2.3.4.4b H5 isolate. The H5 mRNA-LNP vaccine elicits strong T cell and antibody responses in female mice, including neutralizing antibodies and broadly-reactive anti-HA stalk antibodies. The H5 mRNA-LNP vaccine elicits antibodies at similar levels compared to whole inactivated vaccines in female mice with and without prior H1N1 exposures. Finally, we find that the H5 mRNA-LNP vaccine is immunogenic in male ferrets and prevents morbidity and mortality of animals following 2.3.4.4b H5N1 challenge. Together, our data demonstrate that a monovalent mRNA-LNP vaccine expressing 2.3.4.4b H5 is immunogenic and protective in pre-clinical animal models.

Suggested Citation

  • Colleen Furey & Gabrielle Scher & Naiqing Ye & Lisa Kercher & Jennifer DeBeauchamp & Jeri Carol Crumpton & Trushar Jeevan & Christopher Patton & John Franks & Adam Rubrum & Mohamad-Gabriel Alameh & St, 2024. "Development of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48555-z
    DOI: 10.1038/s41467-024-48555-z
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    References listed on IDEAS

    as
    1. Norbert Pardi & Kaela Parkhouse & Ericka Kirkpatrick & Meagan McMahon & Seth J. Zost & Barbara L. Mui & Ying K. Tam & Katalin Karikó & Christopher J. Barbosa & Thomas D. Madden & Michael J. Hope & Flo, 2018. "Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    2. Sigrid Gouma & Kangchon Kim & Madison E. Weirick & Megan E. Gumina & Angela Branche & David J. Topham & Emily T. Martin & Arnold S. Monto & Sarah Cobey & Scott E. Hensley, 2020. "Middle-aged individuals may be in a perpetual state of H3N2 influenza virus susceptibility," Nature Communications, Nature, vol. 11(1), pages 1-8, December.
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