Fig. 5: Characterizing mixtures with multiple stem antibodies.
From: Harnessing low dimensionality to visualize the antibody–virus landscape for influenza
a, Biophysical model for mixtures of stem antibodies binding competitively to an HA monomer. b, Stem + stem mixtures were measured against the virus panel. Mixture IC50 values are predicted using the neutralization of each individual antibody. The gray shading represents ≤4-fold error, where 1-fold error represents an exact prediction. c, Regions of ≥50% neutralization for a two-antibody mixture (outlined in solid lines) versus the neutralization of each individual antibody (dashed lines). The legend shows the concentration of each antibody in the mixture. d, Using a mixture’s neutralization titers, we predict the number, stoichiometry and neutralization profiles of the stem antibodies within. One such stem + stem mixture is shown (gray antibodies, mixture 8 in Supplementary Fig. 10), together with the predicted decomposition (red). Circles around each antibody represent ≥50% virus neutralization when the total antibody concentration is 10−8.5 M, while factoring in antibody stoichiometry within the mixture (Methods). Average error represents the fold-difference between the collective neutralization predicted by the inferred stem antibodies and the measured neutralization of only the stem antibodies in the mixture, with 〈error〉 = 1 representing exact predictions. e, Mean + s.e.m. for the decomposition of 27 monoclonal antibodies, 11 mixtures containing two antibodies (stem + stem or head + stem) and three mixtures containing three antibodies (head + head + stem or head + stem + stem). The fractions of decompositions that predicted the correct number of stem antibodies are shown above each bar. Experimental noise is ~2-fold (dashed line). f, Examples showing additional mixtures combining two stem antibodies with and without a head antibody (additional decompositions are shown in Supplementary Fig. 10). Neutralization of two nearby antibodies is expanded because either can neutralize a virus, analogous to the solid lines in c. The insets at the top left show the number of head (brown) and stem (gray) antibodies in each mixture.
