Fig. 3: RBD-directed antibodies evolve toward enhanced binding and neutralizing activity.

a, b Fab binding affinities of WT/BA.1 cross-reactive antibodies for recombinant WT and BA.1 RBD antigens, as measured by BLI, are plotted as bivariates for antibodies derived from 1-month¹² (left, n = 164) and 5–6-month (right, n = 280) time points in (a) and summarized as a column dot plot in (b). Median affinities are indicated by black bars and shown below data points. c Proportions of WT/BA.1 cross-reactive antibodies at each time point that show an increased affinity for the BA.1 RBD relative to WT (red shades) or increased affinity for WT RBD (blue shades). Values represent the percentage of antibodies belonging to each of the indicated categories. d, e Potency of antibodies with cross-neutralizing activity against SARS-CoV-2 D614G and BA.1 (neutralization threshold defined as IC₅₀ < 2 µg/ml), as determined by an MLV-based pseudovirus neutralization assay. IC₅₀ values are plotted in (d) as bivariates for antibodies isolated from 1-month¹² (left, n = 86) and 5–6-month (right, n = 132) time points and summarized as column dot plots in (e). Median IC₅₀ values are indicated by black bars and shown below data points. f Proportions of WT/BA.1 cross-neutralizing antibodies at each time point that show increased neutralizing potency against BA.1 (red shades) or D614G (blue shades). Values represent the percentage of antibodies belonging to each of the indicated categories. Statistical comparisons were determined by (b, e) multiple two-tailed Mann–Whitney U–tests without adjustment for multiplicity across time points and two-tailed Wilcoxon matched-pairs rank tests within each time point or (c, f) two-tailed Mann–Whitney U-test. IC₅₀ 50% inhibitory concentration, K_D equilibrium dissociation constant; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001. Source data and full statistical test results are provided as a Source Data file.