Tweet
Emerg Microbes Infect
. 2023 Aug 5;2245921.
doi: 10.1080/22221751.2023.2245921. Online ahead of print. SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters
Biao Zhou 1 2 , Runhong Zhou 1 2 3 , Jasper Fuk-Woo Chan 2 3 4 5 6 , Jianwei Zeng 7 , Qi Zhang 8 , Shuofeng Yuan 2 3 4 5 , Li Liu 1 2 3 , Rémy Robinot 9 , Sisi Shan 8 , Na Liu 1 5 , Jiwan Ge 7 , Hugo Yat-Hei Kwong 1 , Dongyan Zhou 1 2 , Haoran Xu 1 2 , Chris Chung-Sing Chan 2 , Vincent Kwok-Man Poon 2 , Hin Chu 2 3 4 5 , Ming Yue 10 , Ka-Yi Kwan 1 , Chun-Yin Chan 1 , Chris Chun-Yiu Chan 2 , Kenn Ka-Heng Chik 2 , Zhenglong Du 1 , Ka-Kit Au 1 , Haode Huang 1 , Hiu-On Man 1 , Jianli Cao 2 , Cun Li 2 , Ziyi Wang 7 , Jie Zhou 2 3 4 5 , Youqiang Song 10 , Man-Lung Yeung 2 3 4 5 , Kelvin Kai-Wang To 2 3 4 5 , David D Ho 11 , Lisa A Chakrabarti 9 , Xinquan Wang 7 , LinQi Zhang 8 , Kwok-Yung Yuen 2 3 4 5 6 , Zhiwei Chen 1 2 3 4 5
Affiliations
ABSTRACTPrevention 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 led to high amount of infectious viruses and extended damage in NT than controls. Mechanistically, while B8-dIgA failed inhibition of SARS-CoV-2 cell-to-cell transmission, virus might hijack B8-dIgA through dendritic cell-mediated trans-infection of NT epithelia with 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 for SARS-CoV-2 nasal infection and injury.
Keywords: IgA; SARS-CoV-2; antibody-mediated trans-infection; nasal turbinate; neutralizing antibody.
. 2023 Aug 5;2245921.
doi: 10.1080/22221751.2023.2245921. Online ahead of print. SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters
Biao Zhou 1 2 , Runhong Zhou 1 2 3 , Jasper Fuk-Woo Chan 2 3 4 5 6 , Jianwei Zeng 7 , Qi Zhang 8 , Shuofeng Yuan 2 3 4 5 , Li Liu 1 2 3 , Rémy Robinot 9 , Sisi Shan 8 , Na Liu 1 5 , Jiwan Ge 7 , Hugo Yat-Hei Kwong 1 , Dongyan Zhou 1 2 , Haoran Xu 1 2 , Chris Chung-Sing Chan 2 , Vincent Kwok-Man Poon 2 , Hin Chu 2 3 4 5 , Ming Yue 10 , Ka-Yi Kwan 1 , Chun-Yin Chan 1 , Chris Chun-Yiu Chan 2 , Kenn Ka-Heng Chik 2 , Zhenglong Du 1 , Ka-Kit Au 1 , Haode Huang 1 , Hiu-On Man 1 , Jianli Cao 2 , Cun Li 2 , Ziyi Wang 7 , Jie Zhou 2 3 4 5 , Youqiang Song 10 , Man-Lung Yeung 2 3 4 5 , Kelvin Kai-Wang To 2 3 4 5 , David D Ho 11 , Lisa A Chakrabarti 9 , Xinquan Wang 7 , LinQi Zhang 8 , Kwok-Yung Yuen 2 3 4 5 6 , Zhiwei Chen 1 2 3 4 5
Affiliations
- PMID: 37542391
- DOI: 10.1080/22221751.2023.2245921
ABSTRACTPrevention 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 led to high amount of infectious viruses and extended damage in NT than controls. Mechanistically, while B8-dIgA failed inhibition of SARS-CoV-2 cell-to-cell transmission, virus might hijack B8-dIgA through dendritic cell-mediated trans-infection of NT epithelia with 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 for SARS-CoV-2 nasal infection and injury.
Keywords: IgA; SARS-CoV-2; antibody-mediated trans-infection; nasal turbinate; neutralizing antibody.