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

• Main Authors: Chen, B. (Author), Chen, H. (Author), Chen, S. (Author), Gu, C. (Author), Gui, X. (Author), Guo, C. (Author), Jiang, W. (Author), Jiao, S. (Author), Li, G. (Author), Liu, C. (Author), Liu, D. (Author), Wang, A. (Author), Wang, J. (Author), Wang, L. (Author), Wang, M. (Author), Wang, R. (Author), Wang, S. (Author), Wang, W. (Author), Yang, Y. (Author), Yu, X. (Author), Zhang, J. (Author), Zhang, M. (Author)
• Format: Article
• Language: English
• Published: Nature Research 2022
• Subjects: Antibodies, Viral; antibody dependent enhancement; Antibody-Dependent Enhancement; coronavirus spike glycoprotein; COVID-19; human; Humans; SARS-CoV-2; Spike Glycoprotein, Coronavirus; spike protein, SARS-CoV-2; virus antibody
• Online Access: View Fulltext in Publisher
• ISBN: 23993642 (ISSN)
• DOI: 10.1038/s42003-022-03207-0

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. © 2022, The Author(s).