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Multivalent S2 subunit vaccines provide broad protection against Clade 1 sarbecoviruses in female mice

Author

Listed:
  • Peter J. Halfmann

    (University of Wisconsin)

  • Raj S. Patel

    (Georgia Institute of Technology)

  • Kathryn Loeffler

    (Georgia Institute of Technology)

  • Atsuhiro Yasuhara

    (Weill Cornell Medicine)

  • Lee-Ann Velde

    (St. Jude Children’s Research Hospital)

  • Jie E. Yang

    (University of Wisconsin
    University of Wisconsin
    University of Wisconsin)

  • Jordan Chervin

    (Weill Cornell Medicine)

  • Chloe Troxell

    (Weill Cornell Medicine)

  • Min Huang

    (Weill Cornell Medicine)

  • Naiying Zheng

    (Weill Cornell Medicine)

  • Elizabeth R. Wright

    (University of Wisconsin
    University of Wisconsin
    University of Wisconsin)

  • Paul G. Thomas

    (St. Jude Children’s Research Hospital)

  • Patrick C. Wilson

    (Weill Cornell Medicine)

  • Yoshihiro Kawaoka

    (University of Wisconsin
    University of Tokyo
    National Center for Global Health and Medicine Research Institute
    University of Tokyo)

  • Ravi S. Kane

    (Georgia Institute of Technology
    Georgia Institute of Technology)

Abstract

The continuing emergence of immune evasive SARS-CoV-2 variants and the previous SARS-CoV-1 outbreak collectively underscore the need for broadly protective sarbecovirus vaccines. Targeting the conserved S2 subunit of SARS-CoV-2 is a particularly promising approach to elicit broad protection. Here, we describe a nanoparticle vaccine displaying multiple copies of the SARS-CoV-1 S2 subunit. This vaccine alone, or as a cocktail with a SARS-CoV-2 S2 subunit vaccine, protects female transgenic K18-hACE2 mice from challenges with Omicron subvariant XBB as well as several sarbecoviruses identified as having pandemic potential including the bat sarbecovirus WIV1, BANAL-236, and a pangolin sarbecovirus. Challenge studies in female Fc-γ receptor knockout mice reveal that antibody-based cellular effector mechanisms play a role in protection elicited by these vaccines. These results demonstrate that our S2-based vaccines provide broad protection against clade 1 sarbecoviruses and offer insight into the mechanistic basis for protection.

Suggested Citation

  • Peter J. Halfmann & Raj S. Patel & Kathryn Loeffler & Atsuhiro Yasuhara & Lee-Ann Velde & Jie E. Yang & Jordan Chervin & Chloe Troxell & Min Huang & Naiying Zheng & Elizabeth R. Wright & Paul G. Thoma, 2025. "Multivalent S2 subunit vaccines provide broad protection against Clade 1 sarbecoviruses in female mice," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-55824-y
    DOI: 10.1038/s41467-025-55824-y
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