Fig. 6. Correlating protective efficacy and affinity to CSP.
a, b Liver burden results for each mAb in the panel. Two separate experiments were conducted, and mAbs 311 and 317 were included for comparison in each. Liver burden experiments were performed and analyzed as in Fig. 5b. Percent inhibition is relative to naïve (no mAb). A two-sided Mann–Whitney U test was used to compare efficacy of reach mAb relative to naïve (no mAb). Significance: ***p = 0.0006. Adjustments were not made for multiple comparisons. For each group (antibody), N = 7 mice; data points represent individual mice. Error bars represent the geometric mean and SD. c–e Correlation of percent inhibition with apparent affinity of each Fab, as measured by BLI, to NPNA4 (c), NPNA8 (d), and rsCSP (e). Binding to immobilized NPNA4 and rsCSP was measured at 6.25, 12.5, 25, 50, 100, and 200 nM, and binding to immobilized NPNA8 at 12.5, 25, 50, and 100 nM. Binding curves were fit with a 2:1 model and affinity measurements were averaged across all fits (≥4) with R2 ≥ 0.98. f Correlation of percent inhibition with the rate of unbinding (kOFF) from rsCSP in BLI experiments as in (e). See also Table S10. Overall, we observe no correlation of protection with affinity to NPNA4, while we observe modest correlations to longer NPNA repeats (NPNA8 and rsCSP). This indicates that, among IGHV3–33 mAbs, binding avidity to extended repeats is a necessary but insufficient determinant of potency of protection. Source data are provided as a Source Data file.