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

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 and Kin-Hang Kok ()
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Chun-Kit Yuen: The University of Hong Kong
Wan-Man Wong: The University of Hong Kong
Long-Fung Mak: The University of Hong Kong
Joy-Yan Lam: The University of Hong Kong
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
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
Kin-Hang Kok: The University of Hong Kong

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-42349-5

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