Mimic Peptides of HIV1 Epitopes as Vaccines

HIV1表位的模拟肽作为疫苗

• 批准号: 6404233
• 负责人: DARCY B WILSON
• 金额: $ 30万
• 依托单位: MIXTURE SCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6404233
• 关键词: AIDS vaccines; biomimetics; cytotoxic T lymphocyte; gag protein; genetically modified animals; human immunodeficiency virus 1; human subject; human therapy evaluation; laboratory mouse; microorganism immunology; nonhuman therapy evaluation; patient oriented research; synthetic peptide; synthetic vaccines; vaccine development

DESCRIPTION (Provided by Applicant): Despite current aggressive treatment protocols based on powerful drug combinations, the incidence of HIV-1 infection is increasing, from already very large numbers, mainly in developing countries that can least afford these newer drug regimens. The objective of this proposal combines the technologies of T cell immunobiology and synthetic peptide chemistry in a strategy of antigen discovery and optimization to identify individual candidate peptide sequence mimics for HIV-1 gag protein fragments as starting points in the design of preventive and therapeutic vaccines. Individual lines and clones of human cytotoxic T lymphocytes (CTL) having relevant lytic specificity for HIV peptide pulsed target cells will be used to screen very large combinatorial peptide libraries for peptide sequences that best stimulate proliferative, cytokine release, or lytic responses by these CTL clones. Candidate sequences deduced from each clonal scan will be synthesized and each individually assessed for activity on the selecting clone. The most effective peptide sequences will then be made available for ex vivo immunogenicity assessments and for phase I/II toxicity/efficacy clinical trials. Preliminary studies indicate that these library scans identify peptides several orders of magnitude more effective than native peptide ligands used to generate a particular T cell clone, and that these optimized superagonist peptides are effective as vaccines, provoking strong T cell mediated immune responses against native peptide ligands. PROPOSED COMMERCIAL APPLICATION: Not Available

描述（由申请人提供）：尽管目前采取了积极的治疗 基于强效药物组合的方案、HIV-1 感染的发生率 数量已经非常大，但仍在增加，主要是在发展中国家 他们最无力承担这些新的药物治疗方案。本提案的目的 结合了T细胞免疫生物学和合成肽技术 化学在抗原发现和优化策略中的识别 HIV-1 gag 蛋白片段的单个候选肽序列模拟物为 预防性和治疗性疫苗设计的起点。 人细胞毒性 T 淋巴细胞 (CTL) 的个体系和克隆具有 HIV 肽脉冲靶细胞的相关裂解特异性将用于 筛选非常大的组合肽库以查找肽序列 最好地刺激这些 CTL 的增殖、细胞因子释放或裂解反应 克隆。将合成从每次克隆扫描推导出来的候选序列 并单独评估每个克隆对选择克隆的活性。最 然后将获得有效的肽序列用于离体 免疫原性评估和 I/II 期毒性/疗效临床 试验。初步研究表明这些库扫描可识别肽 比用于治疗的天然肽配体有效几个数量级 生成特定的 T 细胞克隆，并且这些优化的超级激动剂 肽作为疫苗是有效的，可激发强大的 T 细胞介导的免疫 针对天然肽配体的反应。 拟议的商业应用： 无法使用