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

tetano

Editor, Senior Moderator
Nat Commun


. 2023 Oct 24;14(1):6762.
doi: 10.1038/s41467-023-42349-5. An interferon-integrated mucosal vaccine provides pan-sarbecovirus protection in small animal models

Chun-Kit Yuen[SUP] #[/SUP][SUP] 1 2 [/SUP], Wan-Man Wong[SUP] #[/SUP][SUP] 1 2 [/SUP], Long-Fung Mak[SUP] #[/SUP][SUP] 1 2 [/SUP], Joy-Yan Lam[SUP] 1 2 [/SUP], Lok-Yi Cheung[SUP] 1 [/SUP], Derek Tsz-Yin Cheung[SUP] 1 [/SUP], Yau-Yee Ng[SUP] 1 [/SUP], Andrew Chak-Yiu Lee[SUP] 1 2 [/SUP], Nanshan Zhong[SUP] 3 [/SUP], Kwok-Yung Yuen[SUP] 1 2 4 [/SUP], Kin-Hang Kok[SUP] 5 6 7 8 [/SUP]



Affiliations
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.


 
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