Fig. 5: Demonstration of synergistic growth inhibitory activity of monoclonal antibodies targeting CyRPA.
From: Heterotypic interactions drive antibody synergy against a malaria vaccine candidate
A Predicted growth inhibitory activity (GIA) based on Bliss additivity (red) compared to measured GIA in blue for a mAb combination where one was held at 30 μg/ml (title) and the other held at 20% GIA (X-axis). Complete dilution curves can be seen in Supplementary Fig. 4A. Combinations were measured twice with a single representative experiment shown here. Bar indicates the mean across triplicate measurements. B Heat map summary of the fold improvement over Bliss additivity from panel (A). C SPR sensorgrams of Cy.003 and Cy.007 binding to CyRPA and Fab:CyRPA complexes of Cy.002, Cy.004, or Cy.009 in TBS with 1 mM CaCl2. The black lines indicate the measured response while red lines indicate the curve fit. Each graph shows a five-step two-fold dilution curve starting from 500 nM. D GIA of Cy.009 compared to that of a Cy.003/Cy.009 1:1 mixture (i.e., 1 mg/ml = 1 mg/ml Cy.009 or 0.5 mg/ml Cy.009 + 0.5 mg/ml Cy.003). Each individual point is the mean of a triplicate measurement with error bars indicating the standard deviation. n = 5 and n = 6 independent experiments of complete dilution curves for Cy.009 and Cy.003/Cy.009 respectively. Curve fit used a four-parameter dose-response curve with the upper bound constrained to 100% GIA. EC50 shift determined through extra-sum-of-squares F test (F = 77.68, DFn = 1, DFd = 80), p < 0.0001. E Summary of changes in dissociation rate constant (kd) for SPR data shown in (C). Horizontal line indicates the mean and error bars show the standard deviation across n = 2 independent experiments.
