Extended Data Fig. 1: Utilization of DMS data and comparison of DMS-derived fold resistances with titer changes from mono- and polyclonal sera.
a. Theoretical binding curve of an antibody a to a wild-type epitope of SARS-CoV-2 (black line) and corresponding binding curve to an epitope that is mutated at site s (red line). The black dot and red circle mark the concentrations (x-axis) where the binding is half maximal (y-axis) for the wild type IC50DMS(a) and mutant virus IC50DMS(a,s) respectively. The ‘fold resistance’ (red-black dashed line) denotes the shift in the IC50, such that IC50DMS(a,s) = FR(a, s) · IC50DMS(a). The red square marks the DMS-measured unbound fraction (escape fraction ef(s, a)) and the upward-pointing grey arrow the concentration at which the DMS experiment was conducted. Both, IC50DMS(a), ef(s, a) were measured in the original DMS experiment at an antibody concentration of 400 μg/mL. However, the same DMS experiment, performed with a more- (panel b.) or less (panel c.) potent antibody would yield a smaller, respectively bigger escape fraction, while the phenotypic effect FR(a, s) of the mutation s is quantitatively identical. To avoid these artifacts, we calculated FR(a, s) from the original DMS data. d. Comparison between DMS-derived fold resistances FRx,y and fold resistances derived from neutralization assays (mono-clonal). Distinct markers show the epitope classes and distinct colors the Spike-pseudo-groups. e-g. Comparison between DMS-derived changes in neutralization and neutralization titer changes (polyclonal sera). Geometric mean change in neutralization titers for Alpha (e.), Delta (f.) and BA.2 (g.) after exposure to the Wuhan antigen are highlighted by dots (± standard deviation), whereas DMS-based model predictions are shown as a blue vertical line and were computed as outlined in17,62. Raw data on neutralization titer changes21,63,64,65,66,67,68,69,70,71,72,73. h. Normalized antibody pharmacokinetics after antigen exposure. Parameters and equations given in the Methods section.
