Breadth and magnitude of antigen-specific antibody responses in the control of plasma viremia in simian immunodeficiency
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RESEARCH
Open Access
Breadth and magnitude of antigen-specific antibody responses in the control of plasma viremia in simian immunodeficiency virus infected macaques Bapi Pahar1,2* , Carys S. Kenway-Lynch1, Preston Marx3, Sudesh K. Srivastav4, Celia LaBranche5, David C. Montefiori5 and Arpita Das3
Abstract 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 SIVMAC251. 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. Keywords: Antibody, Breadth, Correlate of protection, Neutralizing antibodies, Peptides, Rhesus macaque, SIV, SIV-antigens
Background HIV-1 infection is associated with polyclonal B-cell activation, hypergammaglobulinemia, the presence of immature/ transitional CD10+ or exhausted CD27 negative B-cells in blood [1, 2], exhaustion of tissue-like memory (CD20(hi)/ CD27(−)/CD21(lo)) B-cells [3], loss of total B-cell populations [4, 5], and nonspecific switching from IgM to IgG, IgA and IgE responses. Our recent data demonstrated * Correspondence: [email protected] 1 Division of Comparative Pathology, Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA 70433, USA 2 Tulane University School of Medicine, New Orleans 70112, LA, USA Full list of author information is available at the end of the article
defective memory (CD21 + CD27+) B-cell proliferation in selective tissues in simian immunodeficiency virus (SIV)infected macaques [6, 7]. Therefore, the maintenance of normal and effective humoral immune responses may
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