Emerging Microbes and Infections (Dec 2023)

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
https://doi.org/10.1080/22221751.2023.2245921
Journal volume & issue
Vol. 12, no. 2

Abstract

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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.

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