Cell Reports
Volume 34, Issue 5, 2 February 2021, 108699
Journal home page for Cell Reports

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

https://doi.org/10.1016/j.celrep.2021.108699Get rights and content
Under a Creative Commons license
open access

Highlights

  • Antibodies against SARS-CoV-2 S protein are isolated from an elite neutralizer

  • Receptor-binding domain (RBD) antibodies target four groups of non-overlapping epitopes

  • Group IV antibodies induce antibody-dependent enhancement (ADE) of entry in Raji cells

  • Group II/III antibodies neutralize SARS-CoV-2 without mediating ADE of entry in vitro

Summary

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-2
SARS-CoV-1
receptor-binding domain epitope
neutralizing activity
antibody-dependent enhancement

Cited by (0)

9

These authors contributed equally

10

Lead contact