Fig. 3: Breadth and escapability among RBM antibodies.

a, Escape mutations in spike-expressing VSV passaged in the presence of monoclonal antibody. Plot shows effects of indicated mutations on antibody (x-axis) and ACE2 (y-axis) binding²⁶. Mutations are classed according to whether they are accessible by single mutation from the Wuhan-1 strain (single-nt accessible) and those that require multi-nucleotide mutations. b, Neutralization of SARS-CoV-2 variants by S2E12 (spike-pseudotyped VSV on Vero E6 cells), relative to Wuhan-1 D614G, as in Fig. 2d. c, S2E12 breadth of neutralization (spike-pseudotyped VSV on 293T-ACE2 cells). Points represent mean of biological duplicates. d, Replicative fitness of S2E12 escape mutations identified in a on Vero E6 cells. Data are mean ± s.e.m. from triplicate experiments. e, f, Structures of S2E12 Fab (e) and S2D106 Fab (f) bound to SARS-CoV-2 RBD. RBD sites coloured by escape (colour bar, centre). The E484 side chain is included for visualization purposes only but was not included in the final S2D106-bound structure owing to weak density. Max, maximum. g, h, Integrative features of the structural footprints (5 Å cut-off) of S2E12 (g) and S2D106 (h). Sites are ordered by the frequency of observed mutants among SARS-CoV-2 sequences on GISAID. Heat maps as in Fig. 2b. Logo plots as in Fig. 1c, but showing only amino acid mutations accessible via single-nucleotide mutation from Wuhan-1 strain for comparison with a. Bar plots illustrate frequency of SARS-CoV-2 mutants and their validated effects on antibody neutralization (spike-pseudotyped VSV on Vero E6 cells). Red indicates greater than tenfold increase in IC₅₀ due to mutation. ND, not determined.