• Yunjiao Zhou, Zezhong Liu, Shibo Li, Wei Xu, Qianqian Zhang, Israel T Silva, Cheng Li, Yanling Wu, Qingling Jiang, Zhenmi Liu, Qiujing Wang, Yu Guo, Jianbo Wu, Chengjian Gu, Xia Cai, Di Qu, Christian T Mayer, Xiangxi Wang, Shibo Jiang, Tianlei Ying, Zhenghong Yuan, Youhua Xie, Yumei Wen, Lu Lu, and Qiao Wang.
• Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Biosafety Level 3 Laboratory, Shanghai Medical College, Fudan University, Shanghai 200032, China.
• Cell Rep. 2021 Feb 2; 34 (5): 108699.

AbstractSeveral potent neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus have been identified. However, antibody-dependent enhancement (ADE) has not been comprehensively studied for SARS-CoV-2, and the relationship between enhancing versus neutralizing activities and antibody epitopes remains unknown. Here, we select a convalescent individual with potent IgG neutralizing activity and characterize his antibody response. Monoclonal antibodies isolated from memory B cells target four groups of five non-overlapping receptor-binding domain (RBD) epitopes. Antibodies to one group of these RBD epitopes mediate ADE of entry in Raji cells via an Fcγ receptor-dependent mechanism. In contrast, antibodies targeting two other distinct epitope groups neutralize SARS-CoV-2 without ADE, while antibodies against the fourth epitope group are poorly neutralizing. One antibody, XG014, potently cross-neutralizes SARS-CoV-2 variants, as well as SARS-CoV-1, with respective IC50 (50% inhibitory concentration) values as low as 5.1 and 23.7 ng/mL, while not exhibiting ADE. Therefore, neutralization and ADE of human SARS-CoV-2 antibodies correlate with non-overlapping RBD epitopes.Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

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