Mimic Peptides of HIV-1 Epitopes as Vaccines

描述(由申请人提供)：尽管目前正在接受积极的治疗 基于强大药物组合的方案，HIV-1感染的发生率 正在增加，从已经很大的数字，主要是在发展中国家 最负担不起这些新的药物疗法的人。这项提议的目的是 结合T细胞免疫生物学和合成肽技术 化学在抗原发现和优化识别策略中的应用 HIV-1 Gag蛋白片段的单个候选多肽序列模拟为 预防和治疗性疫苗设计的起点。 人细胞毒性T淋巴细胞(CTL)的单株和克隆 HIV多肽冲击靶细胞的相关裂解特异性将用于 筛选具有以下特点的超大型组合多肽文库 这些CTL最好地刺激增殖、细胞因子释放或裂解反应 克隆人。从每个克隆扫描中推导出的候选序列将被合成 并且每个单独评估在所选择的克隆上的活动。最多的 然后，有效的多肽序列将可用于体外实验 免疫原性评估和I/II期毒性/疗效临床 审判。初步研究表明，这些文库扫描识别多肽 比天然多肽配体有效几个数量级 产生特定的T细胞克隆，这些优化的超级激动剂 多肽作为疫苗有效，可激发强大的T细胞介导的免疫 对天然多肽配体的反应。 建议的商业应用： 不可用

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