Predicting HIV-1 transmission and antibody neutralization efficacy in vivo from stoichiometric parameters
Fig 2
Estimating the stoichiometry of HIV-1 nAb neutralization (N) with mixed trimer assays.
(A) Scheme depicting the combined experimental-mathematical approach employed here to estimate N. (B) Neutralization by nAb 2F5 of mixed trimer HIV-1 pseudovirus stocks containing the indicated ratios of JR-FL wt (2F5 sensitive) and JR-FL D664N (2F5 resistant) Envs. The relative infectivity (RI) of each stock is given by the percentage of target cell infection (i.e., the inverse of % neutralization) under saturating 2F5 nAb concentrations. (C) Theoretical model predictions of the relation between N (N = 1, 2 or 3; colored lines) and RI of virus stocks with different fractions of neutralization-sensitive to resistant Env (fR). The experimental JR-FL nAb 2F5 RI data from (B) are plotted as black dots, representing two independent experiments. Data fitting resulted in an estimate of N = 1, assuming T = 2 and trimers for each JR-FL virion (S3 Table). (D) Robustness analysis for the N = 1 estimate of HIV-1 strain JR-FL and nAb 2F5 against variation in T and
. Blue areas show combinations of T and
resulting in estimates of N = 1, green areas show combinations of T and
that would result in estimates of N = 2. The actual values of T and
for JR-FL (see above) are marked by the white dot, indicating that the N = 1 estimate is robust. (E) Since the model fit shown in (C) for JR-FL and nAb 2F5 is imperfect, we analyzed the goodness-of-fit. A slightly reduced
or slightly increased T compared to those used for the analysis (white dot, S3 Table) could improve the model fit to the experimental data.