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Optimization of the EC26-2A4 Epitope in the gp41 Membrane Proximal External Region Targeted by Neutralizing Antibodies from an Elite Controller
The analysis of patient derived HIV neutralizing antibodies (nAbs) and their target epitopes in the viral envelope (Env) protein provides important basic information for vaccine design. In this study we optimized an epitope, EC26-2A4, that is targeted by neutralizing antibodies from an elite control...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Mary Ann Liebert, Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899297/ https://www.ncbi.nlm.nih.gov/pubmed/29262692 http://dx.doi.org/10.1089/aid.2017.0250 |
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author | Ringel, Oliver Müller, Karsten Koch, Joachim Brill, Boris Wolf, Timo Stephan, Christoph Vieillard, Vincent Debré, Patrice Dietrich, Ursula |
author_facet | Ringel, Oliver Müller, Karsten Koch, Joachim Brill, Boris Wolf, Timo Stephan, Christoph Vieillard, Vincent Debré, Patrice Dietrich, Ursula |
author_sort | Ringel, Oliver |
collection | PubMed |
description | The analysis of patient derived HIV neutralizing antibodies (nAbs) and their target epitopes in the viral envelope (Env) protein provides important basic information for vaccine design. In this study we optimized an epitope, EC26-2A4, that is targeted by neutralizing antibodies from an elite controller (EC26) and localizes in the membrane-proximal external region from the gp41 transmembrane protein. Due to its overlap with the epitope of the first generation broadly neutralizing monoclonal Ab (mAb) 2F5 associated with autoreactivity, we first defined the minimal core epitope reacting with antibodies from EC26 plasma, but not with mAb 2F5. The optimized minimal epitope, EC26-2A4ΔM, was able to induce neutralizing antibodies in vaccinated mice. We further analyzed the frequency of antibodies against the EC26-2A4ΔM peptide in HIV-positive patient sera from a treated cohort and an untreated long-term nonprogressor (LTNP) cohort. Interestingly, 27% of the LTNP sera reacted with the peptide, whereas only 9% showed reactivity in the treated cohort. Although there was no association between the presence of antibodies against the EC26-2A4ΔM epitope and viral load or CD4 count in these patients, the CD4 nadir in the treated cohort was higher in patients positive for EC26-2A4ΔM antibodies, in particular in patients having such antibodies at an early and a late timepoint after infection. |
format | Online Article Text |
id | pubmed-5899297 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Mary Ann Liebert, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-58992972018-04-16 Optimization of the EC26-2A4 Epitope in the gp41 Membrane Proximal External Region Targeted by Neutralizing Antibodies from an Elite Controller Ringel, Oliver Müller, Karsten Koch, Joachim Brill, Boris Wolf, Timo Stephan, Christoph Vieillard, Vincent Debré, Patrice Dietrich, Ursula AIDS Res Hum Retroviruses Vaccines The analysis of patient derived HIV neutralizing antibodies (nAbs) and their target epitopes in the viral envelope (Env) protein provides important basic information for vaccine design. In this study we optimized an epitope, EC26-2A4, that is targeted by neutralizing antibodies from an elite controller (EC26) and localizes in the membrane-proximal external region from the gp41 transmembrane protein. Due to its overlap with the epitope of the first generation broadly neutralizing monoclonal Ab (mAb) 2F5 associated with autoreactivity, we first defined the minimal core epitope reacting with antibodies from EC26 plasma, but not with mAb 2F5. The optimized minimal epitope, EC26-2A4ΔM, was able to induce neutralizing antibodies in vaccinated mice. We further analyzed the frequency of antibodies against the EC26-2A4ΔM peptide in HIV-positive patient sera from a treated cohort and an untreated long-term nonprogressor (LTNP) cohort. Interestingly, 27% of the LTNP sera reacted with the peptide, whereas only 9% showed reactivity in the treated cohort. Although there was no association between the presence of antibodies against the EC26-2A4ΔM epitope and viral load or CD4 count in these patients, the CD4 nadir in the treated cohort was higher in patients positive for EC26-2A4ΔM antibodies, in particular in patients having such antibodies at an early and a late timepoint after infection. Mary Ann Liebert, Inc. 2018-04-01 2018-04-01 /pmc/articles/PMC5899297/ /pubmed/29262692 http://dx.doi.org/10.1089/aid.2017.0250 Text en © Oliver Ringel et al. 2018; Published by Mary Ann Liebert, Inc. This article is available under the Creative Commons License CC-BY-NC (http://creativecommons.org/licenses/by-nc/4.0). This license permits non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited. Permission only needs to be obtained for commercial use and can be done via RightsLink. |
spellingShingle | Vaccines Ringel, Oliver Müller, Karsten Koch, Joachim Brill, Boris Wolf, Timo Stephan, Christoph Vieillard, Vincent Debré, Patrice Dietrich, Ursula Optimization of the EC26-2A4 Epitope in the gp41 Membrane Proximal External Region Targeted by Neutralizing Antibodies from an Elite Controller |
title | Optimization of the EC26-2A4 Epitope in the gp41 Membrane Proximal External Region Targeted by Neutralizing Antibodies from an Elite Controller |
title_full | Optimization of the EC26-2A4 Epitope in the gp41 Membrane Proximal External Region Targeted by Neutralizing Antibodies from an Elite Controller |
title_fullStr | Optimization of the EC26-2A4 Epitope in the gp41 Membrane Proximal External Region Targeted by Neutralizing Antibodies from an Elite Controller |
title_full_unstemmed | Optimization of the EC26-2A4 Epitope in the gp41 Membrane Proximal External Region Targeted by Neutralizing Antibodies from an Elite Controller |
title_short | Optimization of the EC26-2A4 Epitope in the gp41 Membrane Proximal External Region Targeted by Neutralizing Antibodies from an Elite Controller |
title_sort | optimization of the ec26-2a4 epitope in the gp41 membrane proximal external region targeted by neutralizing antibodies from an elite controller |
topic | Vaccines |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899297/ https://www.ncbi.nlm.nih.gov/pubmed/29262692 http://dx.doi.org/10.1089/aid.2017.0250 |
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