2. Academic Validation
  3. Antibody-dependent enhancement (ADE) of SARS-CoV-2 pseudoviral infection requires FcγRIIB and virus-antibody complex with bivalent interaction

Antibody-dependent enhancement (ADE) of SARS-CoV-2 pseudoviral infection requires FcγRIIB and virus-antibody complex with bivalent interaction

  • Commun Biol. 2022 Mar 24;5(1):262. doi: 10.1038/s42003-022-03207-0.
Shuang Wang  # 1 2,  Junchao Wang  # 3,  Xiaojuan Yu  # 4,  Wen Jiang  # 1,  Shuo Chen  # 5,  Rongjuan Wang  # 1 2,  Mingzhu Wang 3,  Shasha Jiao 1 2,  Yingying Yang 1 2,  Wenbo Wang 4,  Huilin Chen 1,  Ben Chen 1,  Chunying Gu 1,  Chuang Liu 1,  An Wang 1,  Min Wang 1,  Gang Li 1,  Cuicui Guo 1,  Datao Liu 1,  Jinchao Zhang 6,  Min Zhang 7,  Lan Wang 8,  Xun Gui 9
Affiliations

Affiliations

  • 1 Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, 201210, China.
  • 2 Beijing Kohnoor Science & Technology Co., Ltd, Beijing, 102206, China.
  • 3 School of Life Sciences, Anhui University, Hefei, 230601, China.
  • 4 Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, National Institutes for Food and Drug Control, Beijing, 100050, China.
  • 5 Ludwig Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, OX37DQ, United Kingdom.
  • 6 Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, 201210, China. Jinchao.zhang@mabwell.com.
  • 7 School of Life Sciences, Anhui University, Hefei, 230601, China. zhmin07@ahu.edu.cn.
  • 8 Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, National Institutes for Food and Drug Control, Beijing, 100050, China. wanglan@nifdc.org.cn.
  • 9 Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, 201210, China. xun.gui@mabwell.com.
  • # Contributed equally.
PMID: 35332252 DOI: 10.1038/s42003-022-03207-0
Abstract

Understanding the underlying molecular mechanisms behind ADE of SARS-CoV-2 is critical for development of safe and effective therapies. Here, we report that two neutralizing mAbs, MW01 and MW05, could enhance the Infection of SARS-CoV-2 pseudovirus on FcγRIIB-expressing B cells. X-ray crystal structure determination and S trimer-binding modeling showed that MW01 and MW05 could bind to RBDs in S trimer with both "up" and "down" states. While, the neutralizing mAb MW07, which has no ADE activity only binds to RBD in S trimer with "up" state. Monovalent MW01 and MW05 completely diminished the ADE activity compared with their bivalent counterparts. Moreover, both macropinocytosis and endocytosis are confirmed involving in ADE of SARS-CoV-2 pseudoviral Infection. Blocking endosome transportation and lysosome acidification could inhibit the ADE activity mediated by MW05. Together, our results identified a novel ADE mechanism of SARS-CoV-2 pseudovirus in vitro, FcγRIIB-mediated uptake of SARS-CoV-2/mAb complex with bivalent interaction.

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