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

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

doi:10.1080/22221751.2023.2245921

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

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 ChanChris 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

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

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.

Original language	English
Article number	2245921
Journal	Emerging Microbes and Infections
Volume	12
Issue number	2
DOIs	https://doi.org/10.1080/22221751.2023.2245921
Publication status	Published - 2023
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd.

ASJC Scopus Subject Areas

Epidemiology
Parasitology
Microbiology
Immunology
Drug Discovery
Infectious Diseases
Virology

Keywords

IgA
SARS-CoV-2
antibody-mediated trans-infection
nasal turbinate
neutralizing antibody

Access to Document

10.1080/22221751.2023.2245921

Cite this

Zhou, B., Zhou, R., Chan, J. F. W., Zeng, J., Zhang, Q., Yuan, S., Liu, L., Robinot, R., Shan, S., Liu, N., Ge, J., Kwong, H. Y. H., Zhou, D., Xu, H., Chan, C. C. S., Poon, V. K. M., Chu, H., Yue, M., Kwan, K. Y., ... Chen, Z. (2023). SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters¹. Emerging Microbes and Infections, 12(2), Article 2245921. https://doi.org/10.1080/22221751.2023.2245921

Zhou, B, Zhou, R, Chan, JFW, Zeng, J, Zhang, Q, Yuan, S, Liu, L, Robinot, R, Shan, S, Liu, N, Ge, J, Kwong, HYH, Zhou, D, Xu, H, Chan, CCS, Poon, VKM, Chu, H, Yue, M, Kwan, KY, Chan, CY, Chan, CCY, Chik, KKH, Du, Z, Au, KK, Huang, H, Man, HO, Cao, J, Li, C, Wang, Z, Zhou, J, Song, Y, Yeung, ML, To, KKW, Ho, DD, Chakrabarti, LA, Wang, X, Zhang, L, Yuen, KY & Chen, Z 2023, 'SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters¹', Emerging Microbes and Infections, vol. 12, no. 2, 2245921. https://doi.org/10.1080/22221751.2023.2245921

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

abstract = "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.",

keywords = "IgA, SARS-CoV-2, antibody-mediated trans-infection, nasal turbinate, neutralizing antibody",

author = "Biao Zhou and Runhong Zhou and Chan, {Jasper Fuk Woo} and Jianwei Zeng and Qi Zhang and Shuofeng Yuan and Li Liu and R{\'e}my Robinot and Sisi Shan and Na Liu and Jiwan Ge and Kwong, {Hugo Yat Hei} and Dongyan Zhou and Haoran Xu and Chan, {Chris Chung Sing} and Poon, {Vincent Kwok Man} and Hin Chu and Ming Yue and Kwan, {Ka Yi} and Chan, {Chun Yin} and Chan, {Chris Chun Yiu} and Chik, {Kenn Ka Heng} and Zhenglong Du and Au, {Ka Kit} and Haode Huang and Man, {Hiu On} and Jianli Cao and Cun Li and Ziyi Wang and Jie Zhou and Youqiang Song and Yeung, {Man Lung} and To, {Kelvin Kai Wang} and Ho, {David D.} and Chakrabarti, {Lisa A.} and Xinquan Wang and Linqi Zhang and Yuen, {Kwok Yung} and Zhiwei Chen",

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd.",

year = "2023",

doi = "10.1080/22221751.2023.2245921",

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T1 - SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters1

AU - Zhou, Biao

AU - Zhou, Runhong

AU - Chan, Jasper Fuk Woo

AU - Zeng, Jianwei

AU - Zhang, Qi

AU - Yuan, Shuofeng

AU - Liu, Li

AU - Robinot, Rémy

AU - Shan, Sisi

AU - Liu, Na

AU - Ge, Jiwan

AU - Kwong, Hugo Yat Hei

AU - Zhou, Dongyan

AU - Xu, Haoran

AU - Chan, Chris Chung Sing

AU - Poon, Vincent Kwok Man

AU - Chu, Hin

AU - Yue, Ming

AU - Kwan, Ka Yi

AU - Chan, Chun Yin

AU - Chan, Chris Chun Yiu

AU - Chik, Kenn Ka Heng

AU - Du, Zhenglong

AU - Au, Ka Kit

AU - Huang, Haode

AU - Man, Hiu On

AU - Cao, Jianli

AU - Li, Cun

AU - Wang, Ziyi

AU - Zhou, Jie

AU - Song, Youqiang

AU - Yeung, Man Lung

AU - To, Kelvin Kai Wang

AU - Ho, David D.

AU - Chakrabarti, Lisa A.

AU - Wang, Xinquan

AU - Zhang, Linqi

AU - Yuen, Kwok Yung

AU - Chen, Zhiwei

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - IgA

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KW - antibody-mediated trans-infection

KW - nasal turbinate

KW - neutralizing antibody

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