Dataset Information

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.

SUBMITTER: Zhou B

PROVIDER: S-EPMC10444022 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters<sup>1</sup>.

Zhou Biao B Zhou Runhong R Chan Jasper Fuk-Woo JF Zeng Jianwei J Zhang Qi Q Yuan Shuofeng S Liu Li L Robinot Rémy R Shan Sisi S Liu Na N Ge Jiwan J Kwong Hugo Yat-Hei HY Zhou Dongyan D Xu Haoran H Chan Chris Chung-Sing CC Poon Vincent Kwok-Man VK Chu Hin H Yue Ming M Kwan Ka-Yi KY Chan Chun-Yin CY Chan Chris Chun-Yiu CC Chik Kenn Ka-Heng KK Du Zhenglong Z Au Ka-Kit KK Huang Haode H Man Hiu-On HO Cao Jianli J Li Cun C Wang Ziyi Z Zhou Jie J Song Youqiang Y Yeung Man-Lung ML To Kelvin Kai-Wang KK Ho David D DD Chakrabarti Lisa A LA Wang Xinquan X Zhang Linqi L Yuen Kwok-Yung KY Chen Zhiwei Z

Emerging microbes & infections 20231201 2

Prevention of robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) requires <i>in vivo</i> 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 hum ...[more]

PMID: 37542391

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Project description:Despite various attempts to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients with COVID-19 convalescent plasmas, neither appropriate approach nor clinical utility has been established. We examined the efficacy of administration of highly neutralizing COVID-19 convalescent plasma (hn-plasmas) and such plasma-derived IgG administration using the Syrian hamster COVID-19 model. Two hn-plasmas, which were in the best 1% of 340 neutralizing activity-determined convalescent plasmas, were intraperitoneally administered to SARS-CoV-2-infected hamsters, resulting in a significant reduction of viral titers in lungs by up to 32-fold compared to the viral titers in hamsters receiving control nonneutralizing plasma, while with two moderately neutralizing plasmas (mn-plasmas) administered, viral titer reduction was by up to 6-fold. IgG fractions purified from the two hn-plasmas also reduced viral titers in lungs more than those from the two mn-plasmas. The severity of lung lesions seen in hamsters receiving hn-plasmas was minimal to moderate as assessed using microcomputerized tomography, which histological examination confirmed. Western blotting revealed that all four COVID-19 convalescent plasmas variably contained antibodies against SARS-CoV-2 components, including the receptor-binding domain and S1 domain. The present data strongly suggest that administering potent neutralizing activity-confirmed COVID-19 convalescent plasmas would be efficacious in treating patients with COVID-19. IMPORTANCE Convalescent plasmas obtained from patients who recovered from a specific infection have been used as agents to treat other patients infected with the very pathogen. To treat using convalescent plasmas, despite that more than 10 randomized controlled clinical trials have been conducted and more than 100 studies are currently ongoing, the effects of convalescent plasma against COVID-19 remained uncertain. On the other hand, certain COVID-19 vaccines have been shown to reduce the clinical COVID-19 onset by 94 to 95%, for which the elicited SARS-CoV-2-neutralizing antibodies are apparently directly responsible. Here, we demonstrate that highly neutralizing effect-confirmed convalescent plasmas significantly reduce the viral titers in the lung of SARS-CoV-2-infected Syrian hamsters and block the development of virally induced lung lesions. The present data provide a proof of concept that the presence of highly neutralizing antibody in COVID-19 convalescent plasmas is directly responsible for the reduction of viral replication and support the use of highly neutralizing antibody-containing plasmas in COVID-19 therapy with convalescent plasmas.

Dataset Information

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

Publications

SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters<sup>1</sup>.

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Dataset Information

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

Publications

SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters<sup>1</sup>.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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