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
  • 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.
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.

Products