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

[tetano]

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[SUP] 1 [/SUP], Zezhong Liu[SUP] 2 [/SUP], Shibo Li[SUP] 3 [/SUP], Wei Xu[SUP] 1 [/SUP], Qianqian Zhang[SUP] 1 [/SUP], Israel T Silva[SUP] 4 [/SUP], Cheng Li[SUP] 1 [/SUP], Yanling Wu[SUP] 1 [/SUP], Qingling Jiang[SUP] 5 [/SUP], Zhenmi Liu[SUP] 5 [/SUP], Qiujing Wang[SUP] 3 [/SUP], Yu Guo[SUP] 6 [/SUP], Jianbo Wu[SUP] 1 [/SUP], Chengjian Gu[SUP] 1 [/SUP], Xia Cai[SUP] 1 [/SUP], Di Qu[SUP] 1 [/SUP], Christian T Mayer[SUP] 7 [/SUP], Xiangxi Wang[SUP] 8 [/SUP], Shibo Jiang[SUP] 1 [/SUP], Tianlei Ying[SUP] 1 [/SUP], Zhenghong Yuan[SUP] 9 [/SUP], Youhua Xie[SUP] 10 [/SUP], Yumei Wen[SUP] 11 [/SUP], Lu Lu[SUP] 12 [/SUP], Qiao Wang[SUP] 13 [/SUP]



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 IC[SUB]50[/SUB] (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.

 

[Emily]

"Antibodies from our donor bound to five non-overlapping RBD epitopes, similar to other studies reporting three or four distinct antigenic sites within RBD (
Liu et al., 2020a;Robbiani et al., 2020;Rogers et al., 2020;Wec et al., 2020;Wu et al., 2020c;Zost et al., 2020a). Importantly, we found a significant association of ADE with one of five non-overlapping antibody binding RBD epitopes. This was a surprising result given that no such epitope-ADE relationship has ever been reported for coronaviruses to the best of our knowledge. The underlying mechanism warrants further investigation."