tetano
Editor, Senior Moderator
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[SUP] 1 2 [/SUP], Runhong Zhou[SUP] 1 2 3 [/SUP], Jasper Fuk-Woo Chan[SUP] 2 3 4 5 6 [/SUP], Jianwei Zeng[SUP] 7 [/SUP], Qi Zhang[SUP] 8 [/SUP], Shuofeng Yuan[SUP] 2 3 4 5 [/SUP], Li Liu[SUP] 1 2 3 [/SUP], Rémy Robinot[SUP] 9 [/SUP], Sisi Shan[SUP] 8 [/SUP], Na Liu[SUP] 1 5 [/SUP], Jiwan Ge[SUP] 7 [/SUP], Hugo Yat-Hei Kwong[SUP] 1 [/SUP], Dongyan Zhou[SUP] 1 2 [/SUP], Haoran Xu[SUP] 1 2 [/SUP], Chris Chung-Sing Chan[SUP] 2 [/SUP], Vincent Kwok-Man Poon[SUP] 2 [/SUP], Hin Chu[SUP] 2 3 4 5 [/SUP], Ming Yue[SUP] 10 [/SUP], Ka-Yi Kwan[SUP] 1 [/SUP], Chun-Yin Chan[SUP] 1 [/SUP], Chris Chun-Yiu Chan[SUP] 2 [/SUP], Kenn Ka-Heng Chik[SUP] 2 [/SUP], Zhenglong Du[SUP] 1 [/SUP], Ka-Kit Au[SUP] 1 [/SUP], Haode Huang[SUP] 1 [/SUP], Hiu-On Man[SUP] 1 [/SUP], Jianli Cao[SUP] 2 [/SUP], Cun Li[SUP] 2 [/SUP], Ziyi Wang[SUP] 7 [/SUP], Jie Zhou[SUP] 2 3 4 5 [/SUP], Youqiang Song[SUP] 10 [/SUP], Man-Lung Yeung[SUP] 2 3 4 5 [/SUP], Kelvin Kai-Wang To[SUP] 2 3 4 5 [/SUP], David D Ho[SUP] 11 [/SUP], Lisa A Chakrabarti[SUP] 9 [/SUP], Xinquan Wang[SUP] 7 [/SUP], LinQi Zhang[SUP] 8 [/SUP], Kwok-Yung Yuen[SUP] 2 3 4 5 6 [/SUP], Zhiwei Chen[SUP] 1 2 3 4 5 [/SUP]
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[SUP] 1 2 [/SUP], Runhong Zhou[SUP] 1 2 3 [/SUP], Jasper Fuk-Woo Chan[SUP] 2 3 4 5 6 [/SUP], Jianwei Zeng[SUP] 7 [/SUP], Qi Zhang[SUP] 8 [/SUP], Shuofeng Yuan[SUP] 2 3 4 5 [/SUP], Li Liu[SUP] 1 2 3 [/SUP], Rémy Robinot[SUP] 9 [/SUP], Sisi Shan[SUP] 8 [/SUP], Na Liu[SUP] 1 5 [/SUP], Jiwan Ge[SUP] 7 [/SUP], Hugo Yat-Hei Kwong[SUP] 1 [/SUP], Dongyan Zhou[SUP] 1 2 [/SUP], Haoran Xu[SUP] 1 2 [/SUP], Chris Chung-Sing Chan[SUP] 2 [/SUP], Vincent Kwok-Man Poon[SUP] 2 [/SUP], Hin Chu[SUP] 2 3 4 5 [/SUP], Ming Yue[SUP] 10 [/SUP], Ka-Yi Kwan[SUP] 1 [/SUP], Chun-Yin Chan[SUP] 1 [/SUP], Chris Chun-Yiu Chan[SUP] 2 [/SUP], Kenn Ka-Heng Chik[SUP] 2 [/SUP], Zhenglong Du[SUP] 1 [/SUP], Ka-Kit Au[SUP] 1 [/SUP], Haode Huang[SUP] 1 [/SUP], Hiu-On Man[SUP] 1 [/SUP], Jianli Cao[SUP] 2 [/SUP], Cun Li[SUP] 2 [/SUP], Ziyi Wang[SUP] 7 [/SUP], Jie Zhou[SUP] 2 3 4 5 [/SUP], Youqiang Song[SUP] 10 [/SUP], Man-Lung Yeung[SUP] 2 3 4 5 [/SUP], Kelvin Kai-Wang To[SUP] 2 3 4 5 [/SUP], David D Ho[SUP] 11 [/SUP], Lisa A Chakrabarti[SUP] 9 [/SUP], Xinquan Wang[SUP] 7 [/SUP], LinQi Zhang[SUP] 8 [/SUP], Kwok-Yung Yuen[SUP] 2 3 4 5 6 [/SUP], Zhiwei Chen[SUP] 1 2 3 4 5 [/SUP]
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.