Fig. 2: Epitope mapping of monoclonal antibodies by competition-binding analysis and synergistic neutralization by a pair of monoclonal antibodies.

a, Left, monoclonal antibody binding to the S_RBD in the presence of reference monoclonal antibodies COV2-2196 or rCR3022. Values in squares are the per cent binding of the monoclonal antibody in the presence of the competing monoclonal antibody relative to a mock-competition control. Black squares, full competition (<33% relative binding); white squares, no competition (>67% relative binding). Right, biolayer-interferometry-based competition binding assay measuring the ability of monoclonal antibodies to prevent the binding of human ACE2. Values are the per cent blocking of human ACE2 by the monoclonal antibody. Red indicates high blocking activity. b, Competition of the panel of neutralizing monoclonal antibodies with reference monoclonal antibodies COV2-2130, COV2-2196 or rCR3022. Binding of reference monoclonal antibodies to trimeric S2P_ecto was measured in the presence of saturating competitor monoclonal antibody in a competition ELISA and normalized to binding in the presence of r2D22. Black, full competition (<25% binding of reference antibody); grey, partial competition (25–60% binding of reference antibody); white, no competition (>60% binding of reference antibody). c, Neutralization dose–response matrix of wild-type SARS-CoV-2 by COV2-2196 and COV2-2130. Axes denote the concentration of each monoclonal antibody, with the per cent neutralization shown in each square. Data are from a representative experiment performed in technical triplicate and repeated twice. The white-to-red heat map denotes 0% neutralization to 100% neutralization, respectively. d, Synergy map calculated on the basis of the SARS-CoV-2 neutralization in c. δ-score is a synergy score. Red colour indicates areas in which synergistic neutralization was observed; black box indicates the area of maximum synergy between the two monoclonal antibodies.

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