Omicron-specific RBD mutations expand their overall escape of memory B cell-derived antibodies
(A) Dot plot representing the KDs for B.1.1.529 (Omicron) RBD versus ancestral (Hu-1) RBD for all tested monoclonal antibodies from the SARS-CoV-2 recovered (dark blue dots) and naive donors (white dots). The red shaded area indicates monoclonal antibodies with at least two-fold increased KD for B.1.1.529 than for Hu-1 (termed “B.1.1529-affected antibodies” herein) (left panel). Dot plots representing KDs against the B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.1 (Kappa), and B.1.617.2 (Delta) RBD versus the ancestral (Hu-1) RBD for all tested antibodies (right panels). B.1.1.529-affected antibodies are highlighted as larger size red dots (corresponding to clones present in the red sector in the left panel). The percentages indicate the proportion of B.1.1.529-affected monoclonal antibodies also affected by the indicated RBD variant (gray zone).
(B) The frequencies of antibodies targeting one of the predicted essential binding residue groups in the Omicron-affected antibodies (left panel) and in all the tested antibodies (right panel), as defined by RBD variants recognition profile in BLI, among all tested antibodies for each of the 11 individuals from whom memory B cells were assayed. The numbers of monoclonal antibodies for each donor are indicated on top of each histogram in black. The number of antibodies affected by Omicron-specific mutations is detailed in red. S-CoV, patients who recovered from severe COVID-19; M-CoV, patients who recovered from mild COVID-19; Na, patients naive from COVID-19.
(C) The proportion of IGHV1-2, IGHV1-69, IGHV3-30, IGHV3-53, and IGHV3-66 usage among all the tested monoclonal antibodies with available VH sequence and grouped based on their predicted essential binding residues, as defined in (B). The numbers of tested monoclonal antibodies from all donors are indicated on top of each histogram.
(D and E) The ratio of Hu-1 over B.1.1.529 (Omicron) RBD KD (D) or B.1.351 (Beta) over B.1.1.529 (Omicron) KD for all the monoclonal antibodies tested, grouped based on their neutralization potency against D614G (D) or B.1.351 SARS-CoV-2 (E) (refer to Sokal et al., 2021b). The numbers on top indicate the numbers of monoclonal antibodies with a [KD for Hu-1 RBD / KD for B.1.1.529 RBD] ratio <0.5 (D) or a [KD for B.1.351 / KD for B.1.1.529 RBD] ratio <0.5 (E). Values above 10 or below 0.001 were plotted on the axis. See also Table S1.