SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters1

SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters1

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...

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Main Authors: 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
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:Emerging Microbes and Infections
Subjects:
SARS-CoV-2
neutralizing antibody
IgA
nasal turbinate
antibody-mediated trans-infection
Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2023.2245921
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Summary: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.
ISSN:2222-1751

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