Fig. 4: Epitope targeting and evolution of anti-SARS-CoV-2 RBD antibodies. | Nature

Fig. 4: Epitope targeting and evolution of anti-SARS-CoV-2 RBD antibodies.

From: Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection

Fig. 4

a, Schematic of the BLI experiment (left) and IC50 values for randomly selected neutralizing and non-neutralizing antibodies (Ab1 and Ab2) isolated at 1.3 and 12 months after infection (n = 15 antibodies per group, n = 60 antibodies in total). Red horizontal bars indicate geometric mean. Two-sided Mann–Whitney test. b, Dissociation constants (KD) of the n = 30 neutralizing (green) and n = 30 non-neutralizing (red) antibodies shown in a. Horizontal bars indicate geometric mean values. Two-sided Kruskal–Wallis test with subsequent Dunn’s multiple comparisons. BLI traces are shown in Extended Data Fig. 8. c, Heat map of relative inhibition of binding of a monoclonal antibody (Ab2) to preformed complexes of RBD with another monoclonal antibody (Ab1) (grey, no binding; orange, intermediate binding; red, high binding). Data are normalized by subtraction of the autologous antibody control. BLI traces are shown in Extended Data Fig. 9. d, Neutralization of the indicated mutant RBD proteins with antibodies shown in ac. Pie charts illustrate the fraction of antibodies that are poorly or non-neutralizing (IC50 of 100–1,000 ng ml−1, red), intermediate neutralizing (IC50 of 10–100 ng ml−1, pink) and potently neutralizing (IC50 of 0–10 ng ml−1, white) for each mutant. The number in the inner circle shows the number of antibodies tested. e, Graphs show affinities (y-axis) plotted against neutralization activity (x-axis) for 18 clonal antibody pairs isolated 1.3 (top) and 12 months (bottom) after infection (n = 36 antibodies). Spearman correlation test. f, BLI affinity measurements for same n = 36 paired antibodies as in e. Two-tailed Wilcoxon test. g, IC50 values for n = 30 paired neutralizing antibodies isolated at indicated time points versus indicated mutant SARS-CoV-2 pseudoviruses. Antibodies are divided into groups I, II and III (left), on the basis of neutralizing activity: I, potent clonal pairs that do not improve over time; II, clonal pairs that show increased activity over time; and III, clonal pairs showing decreased neutralization activity after 12 months. Antibody class assignment based on initial (1.3 month after infection) sensitivity to mutation is indicated on the right. Red stars indicate antibodies that neutralize all tested RBD mutants. Colour gradient indicates IC50 values ranging from 0 (white) to 1,000 ng ml−1 (red).

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