Mimic Peptides of HIV1 Epitopes as Vaccines

描述（由申请人提供）：尽管目前的积极治疗 基于强效药物组合的治疗方案， 正在增加，从已经非常大的数字，主要是在发展中国家， 那些最不可能负担得起这些新药的人。本提案的目的 结合T细胞免疫生物学和合成肽技术， 抗原发现和优化策略中的化学， HIV-1 gag蛋白片段的单个候选肽序列模拟物， 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）的单个细胞系和克隆， 对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文库中的肽序列， 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的候选序列 并单独评估每种对选择克隆的活性。最 有效的肽序列将可用于离体 免疫原性评估和I/II期毒性/疗效临床试验 审判初步研究表明，这些库扫描识别肽 比天然肽配体更有效几个数量级， 产生一个特定的T细胞克隆，这些优化的超激动剂 肽作为疫苗是有效的，激发强烈的T细胞介导的免疫反应。 针对天然肽配体的反应。 拟定商业应用： 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