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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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Detalles Bibliográficos
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
Descripción
Sumario: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.