Predicting HIV-1 antibody neutralization curves and IC50.

<p>(A) Scheme depicting the virus and nAb-specific parameters necessary to predict HIV-1 neutralization by nAbs <i>in silico</i>. (B) to (D) Predicted HIV-1 nAb neutralization curves in dependence of (B) nAb K_D, (C) HIV-1 entry stoichiometry, T, and (D) mean viron trimer number, . (E) Dependence of nAb IC50 on the number of Env trimers required for HIV-1 cell entry, T. (F) Relation between HIV-1 virion population size and the fraction of Env subunits that need to be bound by nAb to achieve virus population neutralization. (G) Comparison of experimental nAb IC50 values measured with HIV-1 strain BG505 [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006313#ppat.1006313.ref047" target="_blank">47</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006313#ppat.1006313.ref048" target="_blank">48</a>] (<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006313#ppat.1006313.s021" target="_blank">S5 Table</a>) and IC50’s predicted by our model using BG505-specific T, and K_D [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006313#ppat.1006313.ref049" target="_blank">49</a>] values (<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006313#ppat.1006313.s019" target="_blank">S3</a> and <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006313#ppat.1006313.s021" target="_blank">S5</a> Tables). For nAb PGT145 we assumed that only 1 nAb can bind per trimer; the PGT145 IC50 estimates with the 3-nAb-per-trimer model, used for all other nAbs, are shown in light grey (see also panel H). (H) For most nAbs, we assume that three nAbs can bind each trimer, while binding of one nAb is already sufficient for neutralization (N = 1). Binding of nAbs to a trimer that is already neutralized constitutes unproductive binding and may reduce antibody concentrations to a subcritical level [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006313#ppat.1006313.ref027" target="_blank">27</a>]. To quantify this effect, we predicted neutralization by two nAbs with equal K_D, but assuming that either three nAbs can bind each trimer, or that nAb binding is anti-cooperative as observed for PG9/PGT145-like nAbs, which are known to occupy only one of three potential epitopes per trimer. We observed a slight neutralization advantage for PG9/PGT145-like nAb binding behavior, manifested as an approximately two-fold reduction in predicted nAb IC50.