Cell Rep
. 2021 Jan 12;108699.
doi: 10.1016/j.celrep.2021.108699. Online ahead of print.
Enhancement versus neutralization by SARS-CoV-2 antibodies from a convalescent donor associates with distinct epitopes on the RBD
Yunjiao Zhou 1 , Zezhong Liu 2 , Shibo Li 3 , Wei Xu 1 , Qianqian Zhang 1 , Israel T Silva 4 , Cheng Li 1 , Yanling Wu 1 , Qingling Jiang 5 , Zhenmi Liu 5 , Qiujing Wang 3 , Yu Guo 6 , Jianbo Wu 1 , Chengjian Gu 1 , Xia Cai 1 , Di Qu 1 , Christian T Mayer 7 , Xiangxi Wang 8 , Shibo Jiang 1 , Tianlei Ying 1 , Zhenghong Yuan 9 , Youhua Xie 10 , Yumei Wen 11 , Lu Lu 12 , Qiao Wang 13
Affiliations
- PMID: 33485405
- DOI: 10.1016/j.celrep.2021.108699
Abstract
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 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.
Keywords: SARS-CoV-1; SARS-CoV-2; antibody-dependent enhancement; neutralizing activity; receptor-binding domain epitope.
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