Extended Data Fig. 8. Neutralizing activity of bNAb combinations against global heterologous viruses.

(a) Geometric mean IC80 values (µg/ml) of baseline viruses for this study (top) and from Bar-On et al³ (bottom). The participants are ordered according to time to rebound. These data suggest that longer times to rebound were found for those participants whose baseline IC80 < 0.3 µg/ml for at least 2 bNAbs in the therapeutic combination. (b) IC80 values for individual and combination bNAbs. Data are shown as heatmaps with viruses on the rows. Viral subtypes and individual bNAb and bNAb combination IC80 values are shown as columns. Color coding of subtypes and IC80 values is shown on the bottom right. Viruses are ordered according to the number of bNAbs with IC80 < 0.3 µg/ml, with most number of bNAbs active on top and least on the bottom, and according to neutralization sensitivity to each bNAb. The ordering of viruses between the left and the right panels is different. The single bNAb neutralization data for these non-tier-1 374 viruses was obtained from CATNAP, as previously described6, combination IC80 values were predicted using Bliss-Hill model assuming each bNAb at equal concentrations. Combination IC80 values are the sum of concentrations of each bNAb in the combination for predicted 80% neutralization of a given virus. (c) Overall and dual coverage breadth potency curves for VRC07-523LS + PGT121 + PGDM1400 (salmon and red, respectively) and for 3BNC117 + 10-1074 (light and dark blue, respectively). For dual coverage a virus is considered only if it is neutralized by 2 or 3 bNAbs at individual bNAb IC80 < 0.3 µg/ml, based on the suggested trend of this metric associated with longer time of viral control from panel (A). (d) Subtype-specific coverage of single, dual and triple bNAb activity for VRC07-523LS + PGT121 + PGDM1400 (shades of red), and for 3BNC117 + 10-1074 (shades of blue). Single bNAb activity threshold is IC80 < 0.3 µg/ml.