Figure 3.
Determining Omicron-sublineage immune escape using monoclonal antibodies
(A) SARS-CoV-2-neutralizing monoclonal antibodies (n = 158) were derived from 19 studies and ≥43 convalescent individuals. Bar and pie charts indicate numbers of antibodies per heavy-chain variable (VH) gene segment, amino acid (aa) length of the heavy-chain complementarity-determining region 3 (CDRH3), number of VH aa mutations relative to VH germline-encoded domain, and epitope. RBD, receptor-binding domain.
(B) Fractions of antibodies neutralizing Wu01 and Omicron sublineages (IC50 < 10 μg/mL).
(C) Neutralizing antibody IC50s against sublineages (Wu01, n = 158; BA.1, n = 29; BA.1.1, n = 27; BA.2, n = 34; BA.2.12.1, n = 36; BA.4/5, n = 29). Solid lines indicate geometric mean IC50s and 95% confidence intervals, and dashed lines indicate lower (LLOQ, 0.005 μg/mL) and upper limits of quantification (ULOQ, 10 μg/mL). IC50s < LLOQ were imputed to ½ × LLOQ (IC50 = 0.0025).
(D) IC50 heatmap of the subset of antibodies (n = 43) with neutralizing activity (IC50 < 10 μg/mL) against ≥1 Omicron sublineage. Antibodies are sorted based on their potency against BA.1.
(E) Log10 IC50 ratios of antibodies neutralizing any Omicron sublineage for indicated sublineage comparisons. Within each panel, antibodies are sorted by increasing IC50 ratios. Numbers indicate fractions of antibodies with higher, similar, or lower sublineage activity. IC50s < LLOQ were imputed to ½ × LLOQ (IC50 = 0.0025) and IC50s > ULOQ were imputed to 2 × ULOQ (IC50 = 20).
(F) Spearman’s rank correlation coefficients for ≥1 Omicron-sublineage-neutralizing antibodies (n = 43) as shown in Figure S2C. Numbers in bold indicate values with p < 0.05.
(G) VH aa mutations of antibodies neutralizing Wu01 only or both Wu01 and ≥1 Omicron sublineage. Lines indicate medians and interquartile ranges. Groups were compared using a two-tailed Mann-Whitney U test.
(H) Phylogenetic tree and heavy-chain sequence alignment of VH3-53/3-66|VK1-9 public clonotype antibodies. Letters indicate aa mutations relative to VH germline-encoded residues. Number of aa mutations and neutralizing activity are indicated. Germline VH represents consensus of identified antibody germline alleles (VH3-53∗01, VH3-53∗04, and VH3-66∗01).