An interferon-integrated mucosal vaccine provides pan-sarbecovirus protection in small animal models
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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-10-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42349-5 |
| _version_ | 1797557948020424704 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Chun-Kit Yuen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T17:23:27Z |
| format | Article |
| id | doaj.art-7be46c5f05934f0bb145e230a3413bda |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:23:27Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-7be46c5f05934f0bb145e230a3413bda2023-11-20T10:15:24ZengNature PortfolioNature Communications2041-17232023-10-0114111810.1038/s41467-023-42349-5An interferon-integrated mucosal vaccine provides pan-sarbecovirus protection in small animal modelsChun-Kit Yuen0Wan-Man Wong1Long-Fung Mak2Joy-Yan Lam3Lok-Yi Cheung4Derek Tsz-Yin Cheung5Yau-Yee Ng6Andrew Chak-Yiu Lee7Nanshan Zhong8Kwok-Yung Yuen9Kin-Hang Kok10Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Respiratory Medicine, 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 DiseaseDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong KongAbstract 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.https://doi.org/10.1038/s41467-023-42349-5 |
| spellingShingle | 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 An interferon-integrated mucosal vaccine provides pan-sarbecovirus protection in small animal models Nature Communications |
| title | An interferon-integrated mucosal vaccine provides pan-sarbecovirus protection in small animal models |
| title_full | An interferon-integrated mucosal vaccine provides pan-sarbecovirus protection in small animal models |
| title_fullStr | An interferon-integrated mucosal vaccine provides pan-sarbecovirus protection in small animal models |
| title_full_unstemmed | An interferon-integrated mucosal vaccine provides pan-sarbecovirus protection in small animal models |
| title_short | An interferon-integrated mucosal vaccine provides pan-sarbecovirus protection in small animal models |
| title_sort | interferon integrated mucosal vaccine provides pan sarbecovirus protection in small animal models |
| url | https://doi.org/10.1038/s41467-023-42349-5 |
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