A multi-antigen vaccinia vaccine broadly protected mice against SARS-CoV-2 and influenza A virus while also targeting SARS-CoV-1 and MERS-CoV
IntroductionCoronaviruses and influenza viruses are significant respiratory pathogens that cause severe disease burdens and economic losses for society. Due to their diversity and evolution, vaccines typically require periodic updating to remain effective. An additional challenge is imposed by the p...
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Frontiers Media S.A.
2024-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1473428/full |
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| author | Nan Gao Tianhan Yang Lanlan Dong Wanda Tang Kangli Cao Kangli Cao Longfei Ding Cuisong Zhu Shimeng Bai Ai Xia Youwei Zhu Chen Zhao Haoran Peng Jianqing Xu Jianqing Xu Jianqing Xu Jianqing Xu Xiaoyan Zhang Xiaoyan Zhang Xiaoyan Zhang Xiaoyan Zhang |
| author_facet | Nan Gao Tianhan Yang Lanlan Dong Wanda Tang Kangli Cao Kangli Cao Longfei Ding Cuisong Zhu Shimeng Bai Ai Xia Youwei Zhu Chen Zhao Haoran Peng Jianqing Xu Jianqing Xu Jianqing Xu Jianqing Xu Xiaoyan Zhang Xiaoyan Zhang Xiaoyan Zhang Xiaoyan Zhang |
| author_sort | Nan Gao |
| collection | DOAJ |
| description | IntroductionCoronaviruses and influenza viruses are significant respiratory pathogens that cause severe disease burdens and economic losses for society. Due to their diversity and evolution, vaccines typically require periodic updating to remain effective. An additional challenge is imposed by the possible coinfection of SARS-CoV-2 and influenza, which could increase disease severity.MethodsWe developed a vaccinia vaccine, named rTTV-RBD-HA2, broadly targeting coronaviruses and influenza viruses. This vaccine expresses three fusion proteins, each comprising the receptor-binding domain (RBD) from one of the three highly pathogenic coronaviruses (SARS-CoV-2, SARS-CoV, and MERS-CoV) and the conserved HA stalk region from two influenza viruses (pdmH1N1 and nH7N9) belonging to groups 1 and 2, respectively.ResultsThe multi-targeting nature of this vaccine was validated by its success in inducing antibody responses to the three RBDs and both group 1 and 2 HAs in mice. Importantly, it also generated robust T cell responses to all the immunogens, which could be mobilized to the lung through intranasal vaccination. Consistent with this broad immunogenicity profile, when administered via intramuscular priming and two intranasal boosts, rTTV-RBD-HA2 effectively protected vaccinated mice against challenges of the wild-type SARS-CoV-2 virus, the Omicron XBB variant, and the influenza A H1N1 and H3N2 viruses.DiscussionOur results collectively support the candidacy of recombinant rTTV-RBD-HA2 as a novel respiratory virus vaccine that provides cross-protection against coronaviruses and influenza viruses, surpassing the breadth of previous vaccines. Additionally, they underscore the importance of establishing a strong mucosal T cell response in the development of a universal respiratory virus vaccine. |
| format | Article |
| id | doaj-art-c8a5f5842aac4359976357cbe5699bc5 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-c8a5f5842aac4359976357cbe5699bc52025-08-20T02:07:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-11-011510.3389/fimmu.2024.14734281473428A multi-antigen vaccinia vaccine broadly protected mice against SARS-CoV-2 and influenza A virus while also targeting SARS-CoV-1 and MERS-CoVNan Gao0Tianhan Yang1Lanlan Dong2Wanda Tang3Kangli Cao4Kangli Cao5Longfei Ding6Cuisong Zhu7Shimeng Bai8Ai Xia9Youwei Zhu10Chen Zhao11Haoran Peng12Jianqing Xu13Jianqing Xu14Jianqing Xu15Jianqing Xu16Xiaoyan Zhang17Xiaoyan Zhang18Xiaoyan Zhang19Xiaoyan Zhang20Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaDepartment of Microbiology, Second Military Medical University, Shanghai, ChinaClinical Center of Biotherapy at Zhongshan Hospital and Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, ChinaClinical Center for Biotherapy, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, Fujian, ChinaShanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaBio-therapeutic Center, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, The Second Hospital Affiliated with the School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, ChinaShanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaClinical Center of Biotherapy at Zhongshan Hospital and Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaDepartment of Microbiology, Second Military Medical University, Shanghai, ChinaShanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaClinical Center of Biotherapy at Zhongshan Hospital and Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, ChinaClinical Center for Biotherapy, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, Fujian, ChinaXiamen Key Laboratory of Biotherapy, Xiamen, Fujian, ChinaShanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaClinical Center of Biotherapy at Zhongshan Hospital and Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, ChinaClinical Center for Biotherapy, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, Fujian, ChinaXiamen Key Laboratory of Biotherapy, Xiamen, Fujian, ChinaIntroductionCoronaviruses and influenza viruses are significant respiratory pathogens that cause severe disease burdens and economic losses for society. Due to their diversity and evolution, vaccines typically require periodic updating to remain effective. An additional challenge is imposed by the possible coinfection of SARS-CoV-2 and influenza, which could increase disease severity.MethodsWe developed a vaccinia vaccine, named rTTV-RBD-HA2, broadly targeting coronaviruses and influenza viruses. This vaccine expresses three fusion proteins, each comprising the receptor-binding domain (RBD) from one of the three highly pathogenic coronaviruses (SARS-CoV-2, SARS-CoV, and MERS-CoV) and the conserved HA stalk region from two influenza viruses (pdmH1N1 and nH7N9) belonging to groups 1 and 2, respectively.ResultsThe multi-targeting nature of this vaccine was validated by its success in inducing antibody responses to the three RBDs and both group 1 and 2 HAs in mice. Importantly, it also generated robust T cell responses to all the immunogens, which could be mobilized to the lung through intranasal vaccination. Consistent with this broad immunogenicity profile, when administered via intramuscular priming and two intranasal boosts, rTTV-RBD-HA2 effectively protected vaccinated mice against challenges of the wild-type SARS-CoV-2 virus, the Omicron XBB variant, and the influenza A H1N1 and H3N2 viruses.DiscussionOur results collectively support the candidacy of recombinant rTTV-RBD-HA2 as a novel respiratory virus vaccine that provides cross-protection against coronaviruses and influenza viruses, surpassing the breadth of previous vaccines. Additionally, they underscore the importance of establishing a strong mucosal T cell response in the development of a universal respiratory virus vaccine.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1473428/fullcoronavirusSARS-CoV-2influenza virusvaccinia virus Tiantan strainmultipathogen vaccinemucosal immunity |
| spellingShingle | Nan Gao Tianhan Yang Lanlan Dong Wanda Tang Kangli Cao Kangli Cao Longfei Ding Cuisong Zhu Shimeng Bai Ai Xia Youwei Zhu Chen Zhao Haoran Peng Jianqing Xu Jianqing Xu Jianqing Xu Jianqing Xu Xiaoyan Zhang Xiaoyan Zhang Xiaoyan Zhang Xiaoyan Zhang A multi-antigen vaccinia vaccine broadly protected mice against SARS-CoV-2 and influenza A virus while also targeting SARS-CoV-1 and MERS-CoV Frontiers in Immunology coronavirus SARS-CoV-2 influenza virus vaccinia virus Tiantan strain multipathogen vaccine mucosal immunity |
| title | A multi-antigen vaccinia vaccine broadly protected mice against SARS-CoV-2 and influenza A virus while also targeting SARS-CoV-1 and MERS-CoV |
| title_full | A multi-antigen vaccinia vaccine broadly protected mice against SARS-CoV-2 and influenza A virus while also targeting SARS-CoV-1 and MERS-CoV |
| title_fullStr | A multi-antigen vaccinia vaccine broadly protected mice against SARS-CoV-2 and influenza A virus while also targeting SARS-CoV-1 and MERS-CoV |
| title_full_unstemmed | A multi-antigen vaccinia vaccine broadly protected mice against SARS-CoV-2 and influenza A virus while also targeting SARS-CoV-1 and MERS-CoV |
| title_short | A multi-antigen vaccinia vaccine broadly protected mice against SARS-CoV-2 and influenza A virus while also targeting SARS-CoV-1 and MERS-CoV |
| title_sort | multi antigen vaccinia vaccine broadly protected mice against sars cov 2 and influenza a virus while also targeting sars cov 1 and mers cov |
| topic | coronavirus SARS-CoV-2 influenza virus vaccinia virus Tiantan strain multipathogen vaccine mucosal immunity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1473428/full |
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