Fig. 2: Language-model-guided affinity maturation of seven human antibodies.
From: Efficient evolution of human antibodies from general protein language models
a, Strip plots visualizing the two rounds of directed evolution conducted for each antibody. Each point represents an IgG or Fab variant plotted according to the fold change in Kd from wild-type on the y axis and jitter on the x axis; a gray, dashed line is drawn at a fold change of 1, and the wild-type point is colored gray. MEDI8852 variants were screened against HA H4 Hubei; MEDI8852 UCA variants against HA H1 Solomon; mAb114 and mAb114 UCA variants against ebolavirus GP; S309 variants against Wuhan-Hu-1 S-6P; and REGN10987 and C143 variants against Beta S-6P. b, Phylogenetic trees illustrating the evolutionary trajectories from wild-type to the highest-affinity variant(s) of each antibody. Nodes are annotated with the Kd values for different antigens and the Tm of the Fab; all Kd values are for the monovalent Fab versions except those of C143, which are apparent Kd values for the bivalent IgGs. B, Beta; H1 Solo., H1 Solomon; ML variant, machine-learning-guided variant; O, Omicron; W1, Wuhan-Hu-1. c, We obtained avidity and affinity measurements via BLI of IgGs and Fabs at the indicated concentrations binding to the indicated antigen. Selected BLI traces of the highest-affinity variants for the respective antigens are plotted alongside those of the wild-type variants.
