RECOMBINANT MIF AS AN ADJUVANT FOR HIV ANTIGENS

这项提议的目的是确定重组移民是否 抑制因子(RMIF)可增强细胞和体液免疫 对以gp120开始的hiv-1抗原的反应。最近，RMIF一直在 被证明具有与完全弗氏佐剂一样有效的佐剂特性 在以牛血清白蛋白为抗原的小鼠中。在进一步的研究中，RMIF 给带有利什曼原虫抗原(Gp63)的小鼠注射显著增强 它们对随后的寄生虫挑战的保护。 HIV-1抗原将通过RMIF被包裹到脂质体中， 给小鼠注射。将调查以下问题： 1)细胞和免疫：RMIF是否促进T淋巴细胞增殖 对艾滋病毒抗原的影响？产生什么细胞因子(IL-2、IL-4、 干扰素-γ、肿瘤坏死因子α)？是否诱导了细胞毒性T淋巴细胞(CTL)？ 2.)体液免疫和粘膜免疫：诱导哪些亚型抗体 用RMIF吗？抗体中和了吗？它们在ADCC中是否起作用 化验？口服包裹RMIF-HIV-1抗原能否 与羟基磷灰石或其他载体相关的脂质体，可以增强 诱导粘膜免疫球蛋白A？口服抗原是否与RMIF有关 增强对随后的非肠道注射的系统性反应？ 3.)抗原提呈：RMIF能增强抗原提呈吗？是这个吗 对抗原处理的影响？RMIF是否将抗原定向到类型的 APC导致延长免疫力？4)组织病理学：是否存在 注射部位的任何后果的局部炎症反应 脂质体包裹的RMIF和gpl2O。5.)最好的是什么？ 为延长免疫期限而接种疫苗的条件或 二次反应的强度？

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?