SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters 1

作者：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, You‐Qiang Song, Man Lung Yeung, Kelvin Kai‐Wang To, David D. Ho, Lisa A. Chakrabarti, Xinquan Wang, Linqi Zhang, Kwok‐Yung Yuen, Zhiwei Chen · 发表于：Emerging Microbes & Infections · 年份：2023 · DOI：10.1080/22221751.2023.2245921 · 被引用次数：17 · 研究领域：SARS-CoV-2 and COVID-19 Research、Respiratory viral infections research、Immunotherapy and Immune Responses

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.