Predicting HIV-1 transmission and antibody neutralization efficacy in vivo from stoichiometric parameters.
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 interacti...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-05-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC5417720?pdf=render |
| _version_ | 1819128241658527744 |
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| author | Oliver F Brandenberg Carsten Magnus Peter Rusert Huldrych F Günthard Roland R Regoes Alexandra Trkola |
| author_facet | Oliver F Brandenberg Carsten Magnus Peter Rusert Huldrych F Günthard Roland R Regoes Alexandra Trkola |
| author_sort | Oliver F Brandenberg |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T08:24:42Z |
| format | Article |
| id | doaj.art-01aedf74f6ad470a92fa1b1ea7c7d4c1 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-22T08:24:42Z |
| publishDate | 2017-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-01aedf74f6ad470a92fa1b1ea7c7d4c12022-12-21T18:32:40ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742017-05-01135e100631310.1371/journal.ppat.1006313Predicting HIV-1 transmission and antibody neutralization efficacy in vivo from stoichiometric parameters.Oliver F BrandenbergCarsten MagnusPeter RusertHuldrych F GünthardRoland R RegoesAlexandra TrkolaThe 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.http://europepmc.org/articles/PMC5417720?pdf=render |
| spellingShingle | Oliver F Brandenberg Carsten Magnus Peter Rusert Huldrych F Günthard Roland R Regoes Alexandra Trkola Predicting HIV-1 transmission and antibody neutralization efficacy in vivo from stoichiometric parameters. PLoS Pathogens |
| title | Predicting HIV-1 transmission and antibody neutralization efficacy in vivo from stoichiometric parameters. |
| title_full | Predicting HIV-1 transmission and antibody neutralization efficacy in vivo from stoichiometric parameters. |
| title_fullStr | Predicting HIV-1 transmission and antibody neutralization efficacy in vivo from stoichiometric parameters. |
| title_full_unstemmed | Predicting HIV-1 transmission and antibody neutralization efficacy in vivo from stoichiometric parameters. |
| title_short | Predicting HIV-1 transmission and antibody neutralization efficacy in vivo from stoichiometric parameters. |
| title_sort | predicting hiv 1 transmission and antibody neutralization efficacy in vivo from stoichiometric parameters |
| url | http://europepmc.org/articles/PMC5417720?pdf=render |
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