Predicting HIV-1 transmission and antibody neutralization efficacy in vivo from stoichiometric parameters
Abstract
The potential of broadly neutralizing antibodies targeting the HIV-1 envelope trimer to prevent HIV-1 transmission has opened new avenues for therapies and vaccines. However, their implementation remains challenging and would profit from a deepened mechanistic understanding of HIV-antibody interactions and the mucosal transmission process. In this study we experimentally determined stoichiometric parameters of the HIV-1 trimer-antibody interaction, confirming that binding of one antibody is sufficient for trimer neutralization. This defines numerical requirements for HIV-1 virion neutralization and thereby enables mathematical modelling of in vitro and in vivo antibody neutralization efficacy. The model we developed accurately predicts antibody efficacy in animal passive immunization studies and provides estimates for protective mucosal antibody concentrations. Furthermore, we derive estimates of the probability for a single virion to start host infection and the risks of male-to-female HIV-1 transmission per sexual intercourse. Our work thereby delivers comprehensive quantitative insights into both the molecular principles governing HIV-antibody interactions and the initial steps of mucosal HIV-1 transmission. These insights, alongside the underlying, adaptable modelling framework presented here, will be valuable for supporting in silico pre-trial planning and post-hoc evaluation of HIV-1 vaccination or antibody treatment trials. Mehr anzeigen
Persistenter Link
https://doi.org/10.3929/ethz-b-000130816Publikationsstatus
publishedExterne Links
Zeitschrift / Serie
PLoS PathogensBand
Seiten / Artikelnummer
Verlag
PLOSOrganisationseinheit
09490 - Stadler, Tanja / Stadler, Tanja
03584 - Bonhoeffer, Sebastian / Bonhoeffer, Sebastian
Förderung
149769 - Infering virus colonization pathways from high-throughput genetic data (SNF)