Competitive exclusion by autologous antibodies can prevent broad HIV-1 antibodies from arising
Abstract
The past decade has seen the discovery of numerous broad and potent monoclonal antibodies against HIV type 1 (HIV-1). Eliciting these antibodies via vaccination appears to be remarkably difficult, not least because they arise late in infection and are highly mutated relative to germline antibody sequences. Here, using a computational model, we show that broad antibodies could in fact emerge earlier and be less mutated, but that they may be prevented from doing so as a result of competitive exclusion by the autologous antibody response. We further find that this competitive exclusion is weaker in infections founded by multiple distinct strains, with broadly neutralizing antibodies emerging earlier than in infections founded by a single strain. Our computational model simulates coevolving multitype virus and antibody populations. Broadly neutralizing antibodies may therefore be easier for the adaptive immune system to generate than previously thought. As a result, if less mutated broad antibodies exist, it may be possible to elicit them with a vaccine containing a mixture of diverse virus strains.
- Authors:
-
- Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545,, Center for Nonlinear Systems, Los Alamos National Laboratory, Los Alamos, NM 87545
- Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545,
- Publication Date:
- Research Org.:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1579280
- Alternate Identifier(s):
- OSTI ID: 1233530
- Report Number(s):
- LA-UR-15-21719
Journal ID: ISSN 0027-8424
- Grant/Contract Number:
- AC52-06NA25396; R01-AI028433; R01-OD011095; UM1-AI100645
- Resource Type:
- Published Article
- Journal Name:
- Proceedings of the National Academy of Sciences of the United States of America
- Additional Journal Information:
- Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 112 Journal Issue: 37; Journal ID: ISSN 0027-8424
- Publisher:
- Proceedings of the National Academy of Sciences
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; human immunodeficiency virus; broadly neutralizing antibodies; coevolutionary dynamics; mathematical modeling; competitive exclusion
Citation Formats
Luo, Shishi, and Perelson, Alan S. Competitive exclusion by autologous antibodies can prevent broad HIV-1 antibodies from arising. United States: N. p., 2015.
Web. doi:10.1073/pnas.1505207112.
Luo, Shishi, & Perelson, Alan S. Competitive exclusion by autologous antibodies can prevent broad HIV-1 antibodies from arising. United States. https://doi.org/10.1073/pnas.1505207112
Luo, Shishi, and Perelson, Alan S. Mon .
"Competitive exclusion by autologous antibodies can prevent broad HIV-1 antibodies from arising". United States. https://doi.org/10.1073/pnas.1505207112.
@article{osti_1579280,
title = {Competitive exclusion by autologous antibodies can prevent broad HIV-1 antibodies from arising},
author = {Luo, Shishi and Perelson, Alan S.},
abstractNote = {The past decade has seen the discovery of numerous broad and potent monoclonal antibodies against HIV type 1 (HIV-1). Eliciting these antibodies via vaccination appears to be remarkably difficult, not least because they arise late in infection and are highly mutated relative to germline antibody sequences. Here, using a computational model, we show that broad antibodies could in fact emerge earlier and be less mutated, but that they may be prevented from doing so as a result of competitive exclusion by the autologous antibody response. We further find that this competitive exclusion is weaker in infections founded by multiple distinct strains, with broadly neutralizing antibodies emerging earlier than in infections founded by a single strain. Our computational model simulates coevolving multitype virus and antibody populations. Broadly neutralizing antibodies may therefore be easier for the adaptive immune system to generate than previously thought. As a result, if less mutated broad antibodies exist, it may be possible to elicit them with a vaccine containing a mixture of diverse virus strains.},
doi = {10.1073/pnas.1505207112},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 37,
volume = 112,
place = {United States},
year = {Mon Aug 31 00:00:00 EDT 2015},
month = {Mon Aug 31 00:00:00 EDT 2015}
}
https://doi.org/10.1073/pnas.1505207112
Web of Science
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