Predicting HIV-1 transmission and antibody neutralization efficacy in vivo from stoichiometric parameters

PLoS Pathogens

Roland R. Regoes¹  Alexandra Trkola²  Huldrych F. Günthard³  Oliver F. Brandenberg³  Peter Rusert³  Carsten Magnus³ 

[1] Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland;Institute of Integrative Biology, ETH Zurich, Zurich, Switzerland;Institute of Medical Virology, University of Zürich, Zurich, Switzerland

关键词: HIV-1;    Virions;    Antibodies;    Macaque;    Stoichiometry;    Semen;    Viral load;    Viral entry;   

DOI  :  10.1371/journal.ppat.1006313

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY