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Complete mapping of viral escape from neutralizing antibodies

Fig 4

Mutational antigenic profiling of four antibodies.

(A) Each antibody exerts a different profile of selection on HA. (B) Zoomed in view of some of the most strongly selected sites for each antibody. The wild-type amino acid is shown under the logoplots. Sites where mutations were selected in classical escape-mutant selections [11, 12] are underlined. Logoplots spanning all of HA are in S3, S4, S5 and S6 Figs. (C) The selection from each antibody visualized on HA’s structure (PDB 1RVX [54]). Each site is colored from white to red based on the differential selection for the most strongly selected mutation at that site. Red indicates strong differential selection. All structures show trimeric HA in the same orientation (the epitope is visible for two of the three monomers for H17-L19, H17-L7, and H18-S415). See S2 Fig for a zoomed-in structural view. The y-axis scale is set separately for each antibody; since the measured strength of differential selection depends on the concentration / potency of the antibody and the mutational tolerance of the viral epitope, it was impossible to precisely standardize selection strength across antibodies. The scale bar in each logo plot shows the letter height for a mutation with differential selection of 8 (a 256-fold enrichment). The data for each antibody is the average across three biological replicates.

Fig 4