ADJUVANT STRATEGIES USING T CELL HELP ENHANCER PEPTIDES

免疫保护，任何有效疫苗的本质， 通常通过暴露于模拟疾病的试剂而获得 免疫学经验 如果感染了艾滋病 病毒，目前尚不清楚疾病的经验本身的结果， 有效的免疫力可以提供保护。 虽然还不清楚 疾病经历本身会产生有效的免疫力， 保护 作为特异性免疫的一个免疫学参数， 中和抗体的存在，可能与更有利的 短期临床过程中的一些风险组，总的来说，免疫 预防艾滋病的先决条件仍然不明。 的目标 因此，任何潜在的艾滋病疫苗都必须诱导最强的 可能的T细胞和B细胞免疫力在暴露于 艾滋病病毒或感染细胞。 虽然艾滋病的亚单位疫苗 在安全性方面是有吸引力的，这种疫苗通常缺乏 强免疫原性可能对艾滋病疫苗的效力至关重要。 该项目的总体目标是开发通用方法， 增强任何天然或重组抗原的免疫原性， 共价连接小的合成肽，增强T细胞的帮助。 这种新的T细胞辅助增强肽（TEP）佐剂策略将在 追求：1。合成一组适当保护的肽 代表具有良好免疫原性的肽的衍生物 和主要组织相容性（MHC）限制，2.用这些来准备 TEP修饰的蛋白质抗原利用生物化学和免疫学良好 表征的模型抗原和病理重要的gp 160 人免疫缺陷病毒1型的包膜蛋白，3. 比较这些TEP修饰的免疫原性的定量 抗原和对照抗原配制在目前可获得的 佐剂，和4.抗血清的体外抗病毒活性评价 在定量HIV-1抗体检测中针对TAP-gp 160产生。 TEP抗原设计、合成和测试的重复循环应 揭示了增强gp 160免疫原性的方法， 通常适用于其他HIV抗原或任何其他 病理重要性。 在这些研究中开发的TEP-gp 160构建体 研究本身将成为继续临床前和 临床研究。 因此，该项目有可能使 对高免疫原性， 安全有效的艾滋病疫苗。

Immunologic protection, the essence of any effective vaccine, is generally obtained by exposure to an agent that simulates disease experience immunologically. In the case of infection with the AIDS virus, it is not clear that disease experience itself results in effective immunity that could confer protection. Though not clear that disease experience itself results in effective immunity that could confer protection. Though one immunologic parameter of specific immunity, the presence of neutralizing antibody, may correlate with a more favorable short term clinical course in some risk groups, overall, the immunologic prerequisites for protection against AIDS remain unknown. The goal of any potential AIDS vaccine must, therefore, be to induce the strongest possible T cell and B cell immunity in an individual prior to exposure to the AIDS virus or infected cells. While a subunit vaccine for AIDS would be attractive with regard to safety, such vaccines typically lack the strong immunogenicity that may be so critical for AIDS vaccine efficacy. The overall goal of this project is to develop general methods for enhancing the immunogenicity of any native or recombinant antigen by the covalent attachment of small synthetic peptides that enhance T cell help. This novel T cell help enhancer peptide (TEP) adjuvant strategy will be pursued by: 1. Synthesizing a panel of appropriately protected peptide derivatives representing peptides with well characterized immunogenicity and major histocopatibility (MHC) restriction, 2. Using these to prepare TEP-modified protein antigen using biochemically and immunologically well characterized model antigens and the pathologically important gp160 envelope protein of Human Immunodeficiency Virus Type 1, 3. Quantitatively comparing the immunogenicity of these TEP-modified antigens and control antigens formulated in currently available adjuvants, and 4. Evaluating the in vitro antiviral activity of antisera raised against TAP-gp160 in quantitative HIV-1 plaguing assays. Repeated cycles of TEP-antigen design, synthesis, and testing should reveal methods for enhancing the immunogenicity of gp 160 which are generally applicable to other HIV antigens or any other antigen of pathologic importance. The TEP-gp160 constructs developed in these studies will themselves be candidates for continuing preclinical and clinical studies. This project thus has the potential to make substantial contributions to the development of a highly immunogenic, safe and effective vaccine for AIDS.