RECOMBINANT MIF AS AN ADJUVANT FOR HIV ANTIGENS

重组 MIF 作为 HIV 抗原的佐剂

• 批准号: 3548034
• 负责人: JOHN R DAVID
• 金额: $ 20.17万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3548034
• 关键词: AIDS vaccines; HIV envelope protein gp120; T lymphocyte; active immunization; antibody formation; antigen presentation; cell mediated lymphocytolysis test; cytokine; drug design /synthesis /production; histopathology; human immunodeficiency virus 1; human tissue; immunomodulators; injection /infusion; laboratory mouse; liposomes; lymphocyte proliferation; migration inhibition factor; neutralizing antibody; oral administration; tissue /cell culture

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?

本提案的目的是确定重组迁移是否 抑制因子（rMIF）可增强细胞免疫和体液免疫 从gp 120开始对HIV-1抗原的反应。最近，rMIF已被 显示具有与完全弗氏佐剂一样有效佐剂性质 使用牛血清白蛋白作为抗原的小鼠。 在进一步的研究中， 给予小鼠利什曼原虫抗原（gp 63）， 它们对随后的寄生虫攻击的保护。 HIV-1抗原将与rMIF一起包封在脂质体中， 给老鼠服用。将调查以下问题： 1.）的人。细胞与免疫：rMIF是否促进T淋巴细胞增殖 艾滋病毒抗原吗产生什么样的细胞因子（IL-2，IL-4， 干扰素-γ、TNF α）？细胞毒性T淋巴细胞（CTL）是诱导的吗？ 2.）的情况。体液和粘膜免疫：诱导哪些同种型抗体 rMIF？抗体中和了吗？它们是否在ADCC中发挥作用 化验？口服rMIF-HIV-1抗原是否可以 与羟基磷灰石或其他载体结合的脂质体增强了 粘膜伊加的诱导？口服抗原与rMIF 增强对后续胃肠外给药的全身反应？ 3.）第三章抗原呈递：rMIF是否增强抗原呈递？这是 对抗原加工的影响？rMIF是否将抗原导向 APC能延长免疫力？4.）历史学：是否有 注射部位任何后果的局部炎症反应 脂质体包封的rMIF和gp 120。5.）什么是最佳的 免疫接种的条件，以延长免疫的持续时间或 次要反应的强度？