SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters1
ABSTRACTPrevention of robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) requires in vivo evaluation of IgA neutralizing antibodies. Here, we report the efficacy of receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2023-12-01
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| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2023.2245921 |
| _version_ | 1797257028045897728 |
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| author | Biao Zhou Runhong Zhou Jasper Fuk-Woo Chan Jianwei Zeng Qi Zhang Shuofeng Yuan Li Liu Rémy Robinot Sisi Shan Na Liu Jiwan Ge Hugo Yat-Hei Kwong Dongyan Zhou Haoran Xu Chris Chung-Sing Chan Vincent Kwok-Man Poon Hin Chu Ming Yue Ka-Yi Kwan Chun-Yin Chan Chris Chun-Yiu Chan Kenn Ka-Heng Chik Zhenglong Du Ka-Kit Au Haode Huang Hiu-On Man Jianli Cao Cun Li Ziyi Wang Jie Zhou Youqiang Song Man-Lung Yeung Kelvin Kai-Wang To David D. Ho Lisa A. Chakrabarti Xinquan Wang Linqi Zhang Kwok-Yung Yuen Zhiwei Chen |
| author_facet | Biao Zhou Runhong Zhou Jasper Fuk-Woo Chan Jianwei Zeng Qi Zhang Shuofeng Yuan Li Liu Rémy Robinot Sisi Shan Na Liu Jiwan Ge Hugo Yat-Hei Kwong Dongyan Zhou Haoran Xu Chris Chung-Sing Chan Vincent Kwok-Man Poon Hin Chu Ming Yue Ka-Yi Kwan Chun-Yin Chan Chris Chun-Yiu Chan Kenn Ka-Heng Chik Zhenglong Du Ka-Kit Au Haode Huang Hiu-On Man Jianli Cao Cun Li Ziyi Wang Jie Zhou Youqiang Song Man-Lung Yeung Kelvin Kai-Wang To David D. Ho Lisa A. Chakrabarti Xinquan Wang Linqi Zhang Kwok-Yung Yuen Zhiwei Chen |
| author_sort | Biao Zhou |
| collection | DOAJ |
| description | ABSTRACTPrevention of robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) requires in vivo evaluation of IgA neutralizing antibodies. Here, we report the efficacy of receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1, B8-dIgA2 and TH335-dIgA1 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparable neutralization potency against authentic virus by competing with human angiotensin converting enzyme-2 (ACE2) receptor for RBD binding. While reducing viral loads in lungs significantly, prophylactic intranasal B8-dIgA unexpectedly led to high amount of infectious viruses and extended damage in NT compared to controls. Mechanistically, B8-dIgA failed to inhibit SARS-CoV-2 cell-to-cell transmission, but was hijacked by the virus through dendritic cell-mediated trans-infection of NT epithelia leading to robust nasal infection. Cryo-EM further revealed B8 as a class II antibody binding trimeric RBDs in 3-up or 2-up/1-down conformation. Neutralizing dIgA, therefore, may engage an unexpected mode of SARS-CoV-2 nasal infection and injury. |
| first_indexed | 2024-03-08T11:51:59Z |
| format | Article |
| id | doaj.art-06e5de52ccad4802879063fc0fd250b8 |
| institution | Directory Open Access Journal |
| issn | 2222-1751 |
| language | English |
| last_indexed | 2024-04-24T22:31:07Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj.art-06e5de52ccad4802879063fc0fd250b82024-03-19T19:34:17ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512023-12-0112210.1080/22221751.2023.2245921SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters1Biao Zhou0Runhong Zhou1Jasper Fuk-Woo Chan2Jianwei Zeng3Qi Zhang4Shuofeng Yuan5Li Liu6Rémy Robinot7Sisi Shan8Na Liu9Jiwan Ge10Hugo Yat-Hei Kwong11Dongyan Zhou12Haoran Xu13Chris Chung-Sing Chan14Vincent Kwok-Man Poon15Hin Chu16Ming Yue17Ka-Yi Kwan18Chun-Yin Chan19Chris Chun-Yiu Chan20Kenn Ka-Heng Chik21Zhenglong Du22Ka-Kit Au23Haode Huang24Hiu-On Man25Jianli Cao26Cun Li27Ziyi Wang28Jie Zhou29Youqiang Song30Man-Lung Yeung31Kelvin Kai-Wang To32David D. Ho33Lisa A. Chakrabarti34Xinquan Wang35Linqi Zhang36Kwok-Yung Yuen37Zhiwei Chen38AIDS Institute, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaAIDS Institute, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaThe Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing, People’s Republic of ChinaNexVac Research Center, Comprehensive AIDS Research Center, Center for Infectious Diseases, School of Medicine, Tsinghua University, Beijing, People’s Republic of ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaAIDS Institute, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaControl of Chronic Viral Infections Group, Virus & Immunity Unit, Institute Pasteur, Paris, France; CNRS UMR, Paris, FranceNexVac Research Center, Comprehensive AIDS Research Center, Center for Infectious Diseases, School of Medicine, Tsinghua University, Beijing, People’s Republic of ChinaAIDS Institute, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaThe Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing, People’s Republic of ChinaAIDS Institute, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaAIDS Institute, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaAIDS Institute, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaSchool of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaAIDS Institute, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaAIDS Institute, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaAIDS Institute, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaAIDS Institute, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaAIDS Institute, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaAIDS Institute, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaThe Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing, People’s Republic of ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaSchool of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USAControl of Chronic Viral Infections Group, Virus & Immunity Unit, Institute Pasteur, Paris, France; CNRS UMR, Paris, FranceThe Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing, People’s Republic of ChinaNexVac Research Center, Comprehensive AIDS Research Center, Center for Infectious Diseases, School of Medicine, Tsinghua University, Beijing, People’s Republic of ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaAIDS Institute, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of ChinaABSTRACTPrevention of robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) requires in vivo evaluation of IgA neutralizing antibodies. Here, we report the efficacy of receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1, B8-dIgA2 and TH335-dIgA1 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparable neutralization potency against authentic virus by competing with human angiotensin converting enzyme-2 (ACE2) receptor for RBD binding. While reducing viral loads in lungs significantly, prophylactic intranasal B8-dIgA unexpectedly led to high amount of infectious viruses and extended damage in NT compared to controls. Mechanistically, B8-dIgA failed to inhibit SARS-CoV-2 cell-to-cell transmission, but was hijacked by the virus through dendritic cell-mediated trans-infection of NT epithelia leading to robust nasal infection. Cryo-EM further revealed B8 as a class II antibody binding trimeric RBDs in 3-up or 2-up/1-down conformation. Neutralizing dIgA, therefore, may engage an unexpected mode of SARS-CoV-2 nasal infection and injury.https://www.tandfonline.com/doi/10.1080/22221751.2023.2245921SARS-CoV-2neutralizing antibodyIgAnasal turbinateantibody-mediated trans-infection |
| spellingShingle | Biao Zhou Runhong Zhou Jasper Fuk-Woo Chan Jianwei Zeng Qi Zhang Shuofeng Yuan Li Liu Rémy Robinot Sisi Shan Na Liu Jiwan Ge Hugo Yat-Hei Kwong Dongyan Zhou Haoran Xu Chris Chung-Sing Chan Vincent Kwok-Man Poon Hin Chu Ming Yue Ka-Yi Kwan Chun-Yin Chan Chris Chun-Yiu Chan Kenn Ka-Heng Chik Zhenglong Du Ka-Kit Au Haode Huang Hiu-On Man Jianli Cao Cun Li Ziyi Wang Jie Zhou Youqiang Song Man-Lung Yeung Kelvin Kai-Wang To David D. Ho Lisa A. Chakrabarti Xinquan Wang Linqi Zhang Kwok-Yung Yuen Zhiwei Chen SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters1 Emerging Microbes and Infections SARS-CoV-2 neutralizing antibody IgA nasal turbinate antibody-mediated trans-infection |
| title | SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters1 |
| title_full | SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters1 |
| title_fullStr | SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters1 |
| title_full_unstemmed | SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters1 |
| title_short | SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters1 |
| title_sort | sars cov 2 hijacks neutralizing dimeric iga for nasal infection and injury in syrian hamsters1 |
| topic | SARS-CoV-2 neutralizing antibody IgA nasal turbinate antibody-mediated trans-infection |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2023.2245921 |
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