1. Academic Validation
  2. 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. [email protected].
  • 7 School of Life Sciences, Anhui University, Hefei, 230601, China. [email protected].
  • 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. [email protected].
  • 9 Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, 201210, China. [email protected].
  • # Contributed equally.
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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