IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-55824-y.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-55824-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-55824-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Ching-Lin Hsieh & Sarah R. Leist & Emily Happy Miller & Ling Zhou & John M. Powers & Alexandra L. Tse & Albert Wang & Ande West & Mark R. Zweigart & Jonathan C. Schisler & Rohit K. Jangra & Kartik Cha, 2024. "Prefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Jimin Lee & Cameron Stewart & Alexandra Schäfer & Elizabeth M. Leaf & Young-Jun Park & Daniel Asarnow & John M. Powers & Catherine Treichel & Kaitlin R. Sprouse & Davide Corti & Ralph Baric & Neil P. , 2024. "A broadly generalizable stabilization strategy for sarbecovirus fusion machinery vaccines," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Tyler N. Starr & Samantha K. Zepeda & Alexandra C. Walls & Allison J. Greaney & Sergey Alkhovsky & David Veesler & Jesse D. Bloom, 2022. "ACE2 binding is an ancestral and evolvable trait of sarbecoviruses," Nature, Nature, vol. 603(7903), pages 913-918, March.
    4. A. Brenda Kapingidza & Daniel J. Marston & Caitlin Harris & Daniel Wrapp & Kaitlyn Winters & Dieter Mielke & Lu Xiaozhi & Qi Yin & Andrew Foulger & Rob Parks & Maggie Barr & Amanda Newman & Alexandra , 2023. "Engineered immunogens to elicit antibodies against conserved coronavirus epitopes," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    5. Peter J. Halfmann & Kathryn Loeffler & Augustine Duffy & Makoto Kuroda & Jie E. Yang & Elizabeth R. Wright & Yoshihiro Kawaoka & Ravi S. Kane, 2024. "Broad protection against clade 1 sarbecoviruses after a single immunization with cocktail spike-protein-nanoparticle vaccine," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Jun-Yu Si & Yuan-Mei Chen & Ye-Hui Sun & Meng-Xue Gu & Mei-Ling Huang & Lu-Lu Shi & Xiao Yu & Xiao Yang & Qing Xiong & Cheng-Bao Ma & Peng Liu & Zheng-Li Shi & Huan Yan, 2024. "Sarbecovirus RBD indels and specific residues dictating multi-species ACE2 adaptiveness," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Kuan-Ying A. Huang & Xiaorui Chen & Arpita Mohapatra & Hong Thuy Vy Nguyen & Lisa Schimanski & Tiong Kit Tan & Pramila Rijal & Susan K. Vester & Rory A. Hills & Mark Howarth & Jennifer R. Keeffe & Ale, 2023. "Structural basis for a conserved neutralization epitope on the receptor-binding domain of SARS-CoV-2," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Peter J. Halfmann & Kathryn Loeffler & Augustine Duffy & Makoto Kuroda & Jie E. Yang & Elizabeth R. Wright & Yoshihiro Kawaoka & Ravi S. Kane, 2024. "Broad protection against clade 1 sarbecoviruses after a single immunization with cocktail spike-protein-nanoparticle vaccine," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. David Hueting & Karen Schriever & Rui Sun & Stelios Vlachiotis & Fanglei Zuo & Likun Du & Helena Persson & Camilla Hofström & Mats Ohlin & Karin Walldén & Marcus Buggert & Lennart Hammarström & Harold, 2023. "Design, structure and plasma binding of ancestral β-CoV scaffold antigens," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. Xin-Xin Zhu & Wen-Qing Zheng & Zi-Wei Xia & Xin-Ru Chen & Tian Jin & Xu-Wei Ding & Fei-Fei Chen & Qi Chen & Jian-He Xu & Xu-Dong Kong & Gao-Wei Zheng, 2024. "Evolutionary insights into the stereoselectivity of imine reductases based on ancestral sequence reconstruction," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    6. Xandra Nuqui & Lorenzo Casalino & Ling Zhou & Mohamed Shehata & Albert Wang & Alexandra L. Tse & Anupam A. Ojha & Fiona L. Kearns & Mia A. Rosenfeld & Emily Happy Miller & Cory M. Acreman & Surl-Hee A, 2024. "Simulation-driven design of stabilized SARS-CoV-2 spike S2 immunogens," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-55824-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.