ジャーナル: Emerg Microbes Infect / 年: 2023 タイトル: SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters. 著者: 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 ...著者: 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 / Youqiang Song / Man-Lung Yeung / Kelvin Kai-Wang To / David D Ho / Lisa A Chakrabarti / Xinquan Wang / Linqi Zhang / Kwok-Yung Yuen / Zhiwei Chen / 要旨: Prevention of robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) requires evaluation of IgA neutralizing antibodies. Here, we report the efficacy ...Prevention of robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) requires 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.