RECOMBINANT MIF AS AN ADJUVANT FOR HIV ANTIGENS

点击翻译按钮获取中文摘要

The aim of this proposal is to determine whether recombinant migration inhibitory factor (rMIF) will enhance cellular and humoral immune responses to HIV-1 antigens starting with gp120. Recently, rMIF has been shown to have adjuvant properties as potent as complete Freund's adjuvant in mice using bovine serum albumin as antigen. In further studies, rMIF given to mice with a Leishmania parasite antigen (gp63) markedly enhanced their protection to subsequent parasite challenge. HIV-1 antigens will be encapsulated into liposomes with rMIF, administered to mice. The following questions will be investigated: 1.) Cellular and Immunity: Does rMIF enhance T lymphocyte proliferation to HIV-antigens? What cytokines are produced (IL-2, IL-4, interferon-gamma, TNFalpha)? Are cytotoxic T lymphocytes (CTL) induced? 2.) Humoral and Mucosal Immunity: What isotypes of antibodies are induced with rMIF? Are the antibodies neutralizing? Do they function in an ADCC assay? Can the oral administration of rMIF-HIV-1 antigen encapsulated in liposomes, associated with hydroxyapatite or other carriers, enhance the induction of mucosal IgA? Does oral administration of antigen with rMIF enhance a systemic response to a subsequent parenteral administration? 3.) Antigen Presentation: Does rMIF enhance antigen presentation? Is this effect on antigen processing? Does rMIF direct antigens to the type of APC's that lead to prolonged immunity? 4.) Histopathology: Is there a local inflammatory reaction of any consequence at the site of injection of liposome-encapsulated rMIF and gpl2O. 5.) What are the optimum conditions for immunization to prolong the duration of immunity or the intensity of the secondary response?