RT Journal Article
SR Electronic
T1 SARS-CoV-2 hijacks neutralizing dimeric IgA for enhanced nasal infection and injury
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.10.05.463282
DO 10.1101/2021.10.05.463282
A1 Biao Zhou
A1 Runhong Zhou
A1 Jasper Fuk-Woo Chan
A1 Jianwei Zeng
A1 Qi Zhang
A1 Shuofeng Yuan
A1 Li Liu
A1 Rémy Robinot
A1 Sisi Shan
A1 Jiwan Ge
A1 Hugo Yat-Hei Kwong
A1 Dongyan Zhou
A1 Haoran Xu
A1 Chris Chung-Sing Chan
A1 Vincent Kwok-Man Poon
A1 Hin Chu
A1 Ming Yue
A1 Ka-Yi Kwan
A1 Chun-Yin Chan
A1 Na Liu
A1 Chris Chun-Yiu Chan
A1 Kenn Ka-Heng Chik
A1 Zhenglong Du
A1 Ka-Kit Au
A1 Haode Huang
A1 Hiu-On Man
A1 Jianli Cao
A1 Cun Li
A1 Ziyi Wang
A1 Jie Zhou
A1 Youqiang Song
A1 Man-Lung Yeung
A1 Kelvin Kai-Wang To
A1 David D. Ho
A1 Lisa A. Chakrabarti
A1 Xinquan Wang
A1 Linqi Zhang
A1 Kwok-Yung Yuen
A1 Zhiwei Chen
YR 2021
UL http://biorxiv.org/content/early/2021/10/06/2021.10.05.463282.abstract
AB Robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) accounts for high viral transmissibility, yet whether neutralizing IgA antibodies can control it remains unknown. Here, we evaluated receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1 and B8-dIgA2 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparably potent neutralization against authentic virus by competing with human angiotensin converting enzyme-2 (ACE2) receptor for RBD binding. While reducing viruses in lungs, pre-exposure intranasal B8-dIgA1 or B8-dIgA2 led to 81-fold more infectious viruses and severer damage in NT than placebo. Virus-bound B8-dIgA1 and B8-dIgA2 could engage CD209 as an alternative receptor for entry into ACE2-negative cells and allowed viral cell-to-cell transmission. Cryo-EM revealed B8 as a class II neutralizing antibody binding trimeric RBDs in 3-up or 2-up/1-down conformation. Therefore, RBD-specific neutralizing dIgA engages an unexpected action for enhanced SARS-CoV-2 nasal infection and injury in Syrian hamsters.Competing Interest StatementJ.F.W.C. has received travel grants from Pfizer Corporation Hong Kong and Astellas Pharma Hong Kong Corporation Limited and was an invited speaker for Gilead Sciences Hong Kong Limited and Luminex Corporation. The funding sources had no role in study design, data collection, analysis or interpretation or writing of the report. The other authors declare no conflicts of interest except for a provisional patent application filed for human monoclonal antibodies generated in our laboratory.