ADJUVANT STRATEGIES USING T CELL HELP ENHANCER PEPTIDES

使用 T 细胞帮助增强肽的佐剂策略

• 批准号: 3547529
• 负责人: Kemp Bailey Cease
• 金额: $ 12.47万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-08-01 至 1992-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3547529
• 关键词: AIDS; AIDS vaccines; CD4 molecule; antigens; antiviral agents; enzyme linked immunosorbent assay; helper T lymphocyte; human immunodeficiency virus; human immunodeficiency virus 1; immunogenetics; immunological substance; immunomodulators; laboratory mouse; laboratory rabbit; major histocompatibility complex; peptide chemical synthesis; radioimmunoassay; synthetic antigens; virus antigen; virus envelope; virus protein; western blottings

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.

免疫保护是任何有效疫苗的本质 通常通过接触模拟疾病的物质而获得 体验免疫学。 感染艾滋病时 病毒，目前尚不清楚疾病经历本身会导致 可以提供保护的有效免疫力。 虽然不清楚 疾病经历本身会产生有效的免疫力，从而可以赋予 保护。 虽然特异性免疫的一项免疫学参数， 中和抗体的存在可能与更有利的 总体而言，某些危险人群的短期临床病程，免疫学 预防艾滋病的先决条件仍然未知。 目标是 因此，任何潜在的艾滋病疫苗都必须诱导最强的 个体在接触之前可能存在 T 细胞和 B 细胞免疫 艾滋病病毒或受感染的细胞。 虽然艾滋病亚单位疫苗将 在安全性方面具有吸引力，此类疫苗通常缺乏 强大的免疫原性可能对艾滋病疫苗的功效至关重要。 该项目的总体目标是开发通用方法 通过以下方式增强任何天然或重组抗原的免疫原性 小合成肽的共价连接可增强 T 细胞的帮助。 这种新型 T 细胞辅助增强肽 (TEP) 佐剂策略将 追求的目标： 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. 使用这些来准备 TEP修饰的蛋白抗原在生化和免疫学上具有良好的应用 特征模型抗原和病理学上重要的 gp160 人类免疫缺陷病毒 1、3 型的包膜蛋白。 定量比较这些 TEP 修饰的免疫原性 目前可用的抗原和对照抗原 佐剂，以及4.评估抗血清的体外抗病毒活性 在定量 HIV-1 瘟疫检测中针对 TAP-gp160 进行培养。 TEP 抗原设计、合成和测试的重复循环应该 揭示增强 gp 160 免疫原性的方法 通常适用于其他 HIV 抗原或任何其他抗原 病理重要性。 TEP-gp160 构建体在这些中开发 研究本身将成为继续临床前和 临床研究。 因此，该项目有潜力使 对高度免疫原性的开发做出了重大贡献， 安全有效的艾滋病疫苗。