Emerging Microbes and Infections (Dec 2023)
SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters1
- 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
Affiliations
- Biao Zhou
- AIDS 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 China
- Runhong Zhou
- AIDS 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 China
- Jasper Fuk-Woo Chan
- Department 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 China
- Jianwei Zeng
- The 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 China
- Qi Zhang
- NexVac Research Center, Comprehensive AIDS Research Center, Center for Infectious Diseases, School of Medicine, Tsinghua University, Beijing, People’s Republic of China
- Shuofeng Yuan
- Department 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 China
- Li Liu
- AIDS 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 China
- Rémy Robinot
- Control of Chronic Viral Infections Group, Virus & Immunity Unit, Institute Pasteur, Paris, France; CNRS UMR, Paris, France
- Sisi Shan
- NexVac Research Center, Comprehensive AIDS Research Center, Center for Infectious Diseases, School of Medicine, Tsinghua University, Beijing, People’s Republic of China
- Na Liu
- AIDS 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 China
- Jiwan Ge
- The 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 China
- Hugo Yat-Hei Kwong
- AIDS 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 China
- Dongyan Zhou
- AIDS 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 China
- Haoran Xu
- AIDS 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 China
- Chris Chung-Sing Chan
- Department 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 China
- Vincent Kwok-Man Poon
- Department 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 China
- Hin Chu
- Department 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 China
- Ming Yue
- School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of China
- Ka-Yi Kwan
- AIDS 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 China
- Chun-Yin Chan
- AIDS 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 China
- Chris Chun-Yiu Chan
- Department 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 China
- Kenn Ka-Heng Chik
- Department 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 China
- Zhenglong Du
- AIDS 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 China
- Ka-Kit Au
- AIDS 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 China
- Haode Huang
- AIDS 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 China
- Hiu-On Man
- AIDS 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 China
- Jianli Cao
- Department 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 China
- Cun Li
- Department 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 China
- Ziyi Wang
- The 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 China
- Jie Zhou
- Department 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 China
- Youqiang Song
- School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region (SAR), People’s Republic of China
- Man-Lung Yeung
- Department 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 China
- Kelvin Kai-Wang To
- Department 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 China
- David D. Ho
- Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA
- Lisa A. Chakrabarti
- Control of Chronic Viral Infections Group, Virus & Immunity Unit, Institute Pasteur, Paris, France; CNRS UMR, Paris, France
- Xinquan Wang
- The 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 China
- Linqi Zhang
- NexVac Research Center, Comprehensive AIDS Research Center, Center for Infectious Diseases, School of Medicine, Tsinghua University, Beijing, People’s Republic of China
- Kwok-Yung Yuen
- Department 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 China
- Zhiwei Chen
- AIDS 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 China
- DOI
- https://doi.org/10.1080/22221751.2023.2245921
- Journal volume & issue
-
Vol. 12,
no. 2
Abstract
Prevention 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.
Keywords
