| Title | SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters(1). | ||
| Author | Zhou, Biao; Zhou, Runhong; Chan, Jasper Fuk-Woo; Zeng, Jianwei; Zhang, Qi; Yuan, Shuofeng; Liu, Li; Robinot, Remy; Shan, Sisi; Liu, Na; Ge, Jiwan; Kwong, Hugo Yat-Hei; Zhou, Dongyan; Xu, Haoran; Chan, Chris Chung-Sing; Poon, Vincent Kwok-Man; Chu, Hin; Yue, Ming; Kwan, Ka-Yi; Chan, Chun-Yin; Chan, Chris Chun-Yiu; Chik, Kenn Ka-Heng; Du, Zhenglong; Au, Ka-Kit; Huang, Haode; Man, Hiu-On; Cao, Jianli; Li, Cun; Wang, Ziyi; Zhou, Jie; Song, Youqiang; Yeung, Man-Lung; To, Kelvin Kai-Wang; Ho, David D; Chakrabarti, Lisa A; Wang, Xinquan; Zhang, Linqi; Yuen, Kwok-Yung; Chen, Zhiwei | ||
| Journal | Emerg Microbes Infect | Publication Year/Month | 2023-Dec |
| PMID | 37542391 | PMCID | PMC10444022 |
| Affiliation + expend | 1.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. | ||
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.