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An interferon-integrated mucosal vaccine provides pan-sarbecovirus protection in small animal models

Author

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  • Chun-Kit Yuen

    (The University of Hong Kong
    Hong Kong Science and Technology Park)

  • Wan-Man Wong

    (The University of Hong Kong
    Hong Kong Science and Technology Park)

  • Long-Fung Mak

    (The University of Hong Kong
    Hong Kong Science and Technology Park)

  • Joy-Yan Lam

    (The University of Hong Kong
    Hong Kong Science and Technology Park)

  • Lok-Yi Cheung

    (The University of Hong Kong)

  • Derek Tsz-Yin Cheung

    (The University of Hong Kong)

  • Yau-Yee Ng

    (The University of Hong Kong)

  • Andrew Chak-Yiu Lee

    (The University of Hong Kong
    Hong Kong Science and Technology Park)

  • Nanshan Zhong

    (the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, China State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease)

  • Kwok-Yung Yuen

    (The University of Hong Kong
    Hong Kong Science and Technology Park
    The University of Hong Kong)

  • Kin-Hang Kok

    (The University of Hong Kong
    Hong Kong Science and Technology Park
    The University of Hong Kong
    The University of Hong Kong)

Abstract

A pan-sarbecovirus or pan-betacoronavirus vaccine that can prevent current and potential future beta-coronavirus infections is important for fighting possible future pandemics. Here, we report a mucosal vaccine that cross-protects small animal models from sarbecoviruses including SARS-CoV-1, SARS-CoV-2 and its variants. The vaccine comprises a live-but-defective SARS-CoV-2 virus that is envelope deficient and has the orf8 segment replaced by interferon-beta, hence named Interferon Beta Integrated SARS-CoV-2 (IBIS) vaccine. Nasal vaccination with IBIS protected mice from lethal homotypic SARS-CoV-2 infection and hamsters from co-housing-mediated transmission of homotypic virus. Moreover, IBIS provided complete protection against heterotypic sarbecoviruses, including SARS-CoV-2 Delta and Omicron variants, and SARS-CoV-1 in both mice and hamsters. Besides inducing a strong lung CD8 + T cell response, IBIS specifically heightened the activation of mucosal virus-specific CD4 + T cells compared to the interferon-null vaccine. The direct production of interferon by IBIS also suppressed virus co-infection of SARS-CoV-2 in human cells, reducing the risk of genetic recombination when using as live vaccines. Altogether, IBIS is a next-generation pan-sarbecovirus vaccine and warrants further clinical investigations.

Suggested Citation

  • Chun-Kit Yuen & Wan-Man Wong & Long-Fung Mak & Joy-Yan Lam & Lok-Yi Cheung & Derek Tsz-Yin Cheung & Yau-Yee Ng & Andrew Chak-Yiu Lee & Nanshan Zhong & Kwok-Yung Yuen & Kin-Hang Kok, 2023. "An interferon-integrated mucosal vaccine provides pan-sarbecovirus protection in small animal models," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42349-5
    DOI: 10.1038/s41467-023-42349-5
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