UBC Math Bio Seminar: Jonah Brooks Hall

VRC01, VRC01LS, and VRC07-523LS are broadly neutralizing antibodies (bnAbs) that target the CD4 binding site of gp120 on the HIV-1 envelope. VRC01LS and VRC07-523LS are enhanced modifications of the VRC01 and VRC07 antibodies. Phase 1 clinical trials have been performed by the NIH to assess these bnAbs’ safety and effect on viremia in HIV-chronically infected individuals off antiretroviral therapy (ART). After an infusion of a bnAb, most participants had a viral decline of more than 1-log10 followed by a rebound. Here, we fit mathematical models of pharmacokinetics and virus dynamics to serum bnAb concentrations and plasma viral loads from each participant. We assumed two pre-existent viral populations, one sensitive to a given bnAb and one resistant. Our modeling showed that the half-life of VRC01LS and VRC07-523LS was up to four times that of VRC01, but with VRC01LS’ final concentration higher than VRC07-523-LS. We used an in vivo half maximal inhibitory coefficient (IC50) estimated from the model as an indicator of the bnAbs’ relative potency and found that VRC07-523LS is the most effective at neutralization. We also found a higher infected cell death rate for those receiving VRC07-523-LS compared to the other bnAbs or ART, suggesting an Fc-mediated effect. In conclusion, our model recapitulates the antibody and virus dynamics from individuals receiving a bnAb and found VRC07-523LS to have the highest in vivo neutralization potency with a possible Fc-mediated effect.