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

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Brandenberg Oliver F., Magnus Carsten, Rusert Peter, Günthard Huldrych F., Regoes Roland R., Trkola Alexandra,
Project Swiss HIV Cohort Study (SHCS)
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Original article (peer-reviewed)

Journal PLOS Pathogens
Volume (Issue) 13(5)
Page(s) e1006313 - e1006313
Title of proceedings PLOS Pathogens
DOI 10.1371/journal.ppat.1006313

Open Access

URL http://doi.org/10.1371/journal.ppat.1006313
Type of Open Access Publisher (Gold Open Access)

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
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