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Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies

Author

Listed:
  • Norbert Pardi

    (University of Pennsylvania)

  • Kaela Parkhouse

    (University of Pennsylvania)

  • Ericka Kirkpatrick

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

  • Meagan McMahon

    (Icahn School of Medicine at Mount Sinai)

  • Seth J. Zost

    (University of Pennsylvania)

  • Barbara L. Mui

    (Acuitas Therapeutics)

  • Ying K. Tam

    (Acuitas Therapeutics)

  • Katalin Karikó

    (BioNTech RNA Pharmaceuticals)

  • Christopher J. Barbosa

    (Acuitas Therapeutics)

  • Thomas D. Madden

    (Acuitas Therapeutics)

  • Michael J. Hope

    (Acuitas Therapeutics)

  • Florian Krammer

    (Icahn School of Medicine at Mount Sinai)

  • Scott E. Hensley

    (University of Pennsylvania)

  • Drew Weissman

    (University of Pennsylvania)

Abstract

Currently available influenza virus vaccines have inadequate effectiveness and are reformulated annually due to viral antigenic drift. Thus, development of a vaccine that confers long-term protective immunity against antigenically distant influenza virus strains is urgently needed. The highly conserved influenza virus hemagglutinin (HA) stalk represents one of the potential targets of broadly protective/universal influenza virus vaccines. Here, we evaluate a potent broadly protective influenza virus vaccine candidate that uses nucleoside-modified and purified mRNA encoding full-length influenza virus HA formulated in lipid nanoparticles (LNPs). We demonstrate that immunization with HA mRNA-LNPs induces antibody responses against the HA stalk domain of influenza virus in mice, rabbits, and ferrets. The HA stalk-specific antibody response is associated with protection from homologous, heterologous, and heterosubtypic influenza virus infection in mice.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05482-0
    DOI: 10.1038/s41467-018-05482-0
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    Cited by:

    1. 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.
    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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