Fig. 3: Epitope characterization of mAbs elicited by Omicron breakthrough infections.

a–c, FACS analysis of pooled memory B cells (IgM⁻, IgD⁻/CD27⁺) from Omicron breakthrough-infection convalescent individuals. BA.5 breakthrough infection (a), BA.2 breakthrough infection (b) and BA.2 convalescent individuals without vaccination (c) are shown. APC, allophycocyanine; FITC, fluorescein isothiocyanate; PE, phycoerythrin. d, The heavy-chain variable (VH) domain SHM rate of mAbs from individuals with BA.2 (n = 757) and BA.5 (n = 297) breakthrough infection. Binding specificity was determined by ELISA. Statistical tests were determined using two-tailed Wilcoxon rank-sum tests. Boxes display the 25th percentile, median and 75th percentile, and whiskers indicate median ± 1.5 times the interquartile range. Violin plots show kernel density estimation curves of the distribution. Numbers and ratios of samples in each group are labelled above the violin plots. e, t-SNE and clustering of SARS-CoV-2 WT RBD-binding antibodies based on DMS profiles of 3,051 antibodies. f, Epitope distribution of mAbs from convalescent individuals after WT infection or post-vaccination BA.1, BA.2 or BA.5 infection. Numbers in the centre circles indicate total numbers of mAbs. Colours for epitope groups in e also refer to f. Two-tailed binomial tests were used to compare the proportion of each epitope group from BA.2 and BA.5 convalescent individuals with that from BA.1. *P < 0.05, **P < 0.01, ***P < 0.001 and no label for P > 0.05. g, Projection of the neutralizing activity of mAbs against SARS-CoV-2 D614G (left; n = 3,046), BA.2.75 (middle; n = 3,046) and BA.4/5 (right; n = 3,046). h, Projection of the ACE2 competition level of mAbs determined by competition ELISA (n = 1,317). All neutralization assays and ELISA were conducted in at least two independent experiments.