Enhancement versus neutralization by SARS-CoV-2 antibodies from a convalescent donor associates with distinct epitopes on the RBD

• DOI: 10.1016/j.celrep.2021.108699
• Publication Date: 2021-01-14T06:08:55Z
• Authors: 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; Qiao Wang
• Keywords: Adult; Male; 0301 basic medicine; Adolescent; Antibodies, Viral; General Biochemistry, Genetics and Molecular Biology; Article; Cell Line; Antigen-Antibody Reactions; Epitopes; Inhibitory Concentration 50; 03 medical and health sciences; Protein Domains; Cluster Analysis; Humans; Child; Aged; SARS-CoV-2; Antibodies, Monoclonal; COVID-19; Middle Aged; Antibodies, Neutralizing; Antibody-Dependent Enhancement; 3. Good health; Female

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