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Breadth and magnitude of antigen-specific antibody responses in the control of plasma viremia in simian immunodeficiency virus infected macaques

BACKGROUND: Increasing evidence suggests an unexpected potential for non-neutralizing antibodies to prevent HIV infection. Consequently, identification of functional linear B-cell epitopes for HIV are important for developing preventative and therapeutic strategies. We therefore explored the role of...

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Autores principales: Pahar, Bapi, Kenway-Lynch, Carys S., Marx, Preston, Srivastav, Sudesh K., LaBranche, Celia, Montefiori, David C., Das, Arpita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131515/
https://www.ncbi.nlm.nih.gov/pubmed/27903274
http://dx.doi.org/10.1186/s12985-016-0652-x
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author Pahar, Bapi
Kenway-Lynch, Carys S.
Marx, Preston
Srivastav, Sudesh K.
LaBranche, Celia
Montefiori, David C.
Das, Arpita
author_facet Pahar, Bapi
Kenway-Lynch, Carys S.
Marx, Preston
Srivastav, Sudesh K.
LaBranche, Celia
Montefiori, David C.
Das, Arpita
author_sort Pahar, Bapi
collection PubMed
description BACKGROUND: Increasing evidence suggests an unexpected potential for non-neutralizing antibodies to prevent HIV infection. Consequently, identification of functional linear B-cell epitopes for HIV are important for developing preventative and therapeutic strategies. We therefore explored the role of antigen-specific immune responses in controlling plasma viremia in SIV infected rhesus macaques. METHODS: Thirteen rhesus macaques were inoculated either intravaginally or intrarectally with SIV(MAC)251. Peripheral blood CD4+ T-cells were quantified. Plasma was examined for viremia, antigen specific IgG, IgA and IgM binding responses and neutralizing antibodies. Regions containing binding epitopes for antigen-specific IgG, IgM and IgA responses were determined, and the minimum size of linear Envelope epitope responsible for binding antibodies was identified. RESULTS: The presence of neutralizing antibodies did not correlate the outcome of the disease. In a few SIV-infected macaques, antigen-specific IgG and IgM responses in plasma correlated with decreased plasma viremia. Early induction and the breadth of antigen-specific IgG responses were found to be significantly correlated with the control of plasma viral load. Immunoglobulin classes share similar functional linear B-cell epitopes. SIV-specific linear envelope B-cell epitopes were found to be 12 amino-acids in length. CONCLUSIONS: Early induction of combination of peptide-specific IgG responses were found to be responsible for the control of plasma viral load and indicative of disease outcome in SIV-infected rhesus macaques and might be important for the development of therapeutic strategies for control or prevention of HIV/AIDS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0652-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-51315152016-12-15 Breadth and magnitude of antigen-specific antibody responses in the control of plasma viremia in simian immunodeficiency virus infected macaques Pahar, Bapi Kenway-Lynch, Carys S. Marx, Preston Srivastav, Sudesh K. LaBranche, Celia Montefiori, David C. Das, Arpita Virol J Research BACKGROUND: Increasing evidence suggests an unexpected potential for non-neutralizing antibodies to prevent HIV infection. Consequently, identification of functional linear B-cell epitopes for HIV are important for developing preventative and therapeutic strategies. We therefore explored the role of antigen-specific immune responses in controlling plasma viremia in SIV infected rhesus macaques. METHODS: Thirteen rhesus macaques were inoculated either intravaginally or intrarectally with SIV(MAC)251. Peripheral blood CD4+ T-cells were quantified. Plasma was examined for viremia, antigen specific IgG, IgA and IgM binding responses and neutralizing antibodies. Regions containing binding epitopes for antigen-specific IgG, IgM and IgA responses were determined, and the minimum size of linear Envelope epitope responsible for binding antibodies was identified. RESULTS: The presence of neutralizing antibodies did not correlate the outcome of the disease. In a few SIV-infected macaques, antigen-specific IgG and IgM responses in plasma correlated with decreased plasma viremia. Early induction and the breadth of antigen-specific IgG responses were found to be significantly correlated with the control of plasma viral load. Immunoglobulin classes share similar functional linear B-cell epitopes. SIV-specific linear envelope B-cell epitopes were found to be 12 amino-acids in length. CONCLUSIONS: Early induction of combination of peptide-specific IgG responses were found to be responsible for the control of plasma viral load and indicative of disease outcome in SIV-infected rhesus macaques and might be important for the development of therapeutic strategies for control or prevention of HIV/AIDS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0652-x) contains supplementary material, which is available to authorized users. BioMed Central 2016-12-01 /pmc/articles/PMC5131515/ /pubmed/27903274 http://dx.doi.org/10.1186/s12985-016-0652-x Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Pahar, Bapi
Kenway-Lynch, Carys S.
Marx, Preston
Srivastav, Sudesh K.
LaBranche, Celia
Montefiori, David C.
Das, Arpita
Breadth and magnitude of antigen-specific antibody responses in the control of plasma viremia in simian immunodeficiency virus infected macaques
title Breadth and magnitude of antigen-specific antibody responses in the control of plasma viremia in simian immunodeficiency virus infected macaques
title_full Breadth and magnitude of antigen-specific antibody responses in the control of plasma viremia in simian immunodeficiency virus infected macaques
title_fullStr Breadth and magnitude of antigen-specific antibody responses in the control of plasma viremia in simian immunodeficiency virus infected macaques
title_full_unstemmed Breadth and magnitude of antigen-specific antibody responses in the control of plasma viremia in simian immunodeficiency virus infected macaques
title_short Breadth and magnitude of antigen-specific antibody responses in the control of plasma viremia in simian immunodeficiency virus infected macaques
title_sort breadth and magnitude of antigen-specific antibody responses in the control of plasma viremia in simian immunodeficiency virus infected macaques
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131515/
https://www.ncbi.nlm.nih.gov/pubmed/27903274
http://dx.doi.org/10.1186/s12985-016-0652-x
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