Extended Data Fig. 8. Functional activities of WRAIR mAb combinations against SARS-CoV-2 IL1/2020 and characterization of variant binding.
a, Functional activities of NTD/RBD and RBD/RBD mAb combinations. WRAIR-2039, -2025 (NTD) and WRAIR-2123, -2125 and -2173 (RBD) were mixed in a 1:1 ratio as indicated and the cocktail was assessed for neutralization (pSV assay) and Fc effector functions. Single mAbs or cocktail were tested at the same final antibody concentration. IC50 values (µg ml-1) obtained in the pSV assay from 2 independent experiments are indicated in parentheses. ADCD and ADNP activities were measured twice and shown are data from a single representative experiment. The WRAIR-2039 LALA-PG negative control is shown as open circles and dotted blue line. b, Effect of mutations present in VOC and VOI on the binding on-rate and off-rate of NTD-directed mAbs. Binding on-rates (left) and off-rates (right) to stabilized S trimer (S-2P) harboring mutations present in the indicated variant was assessed by BLI. On- and off-rates were obtained by fitting the binding curves of mAbs at a single concentration of 200 nM using a 1:1 binding model. Heat-map shows the log2 fold change relative to a WA1/2020 D614G S-2P spike protein with negatively impacted mAbs (by either a decrease in on-rate or increase in off-rate) represented in shades of red. Shades of blue represent mAb with improved binding kinetics, compared to the WT. NB indicate absence of value due to lack of binding.