DESIGN AND DELIVERY OF HIV CORECEPTOR BASED VACCINE

基于 HIV 受体的疫苗的设计和交付

• 批准号: 2543067
• 负责人: JAMES P TAM
• 金额: $ 26.67万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-01 至 2001-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2543067
• 关键词: AIDS vaccines; active immunization; antireceptor antibody; chemokine; cytokine receptors; laboratory mouse; laboratory rabbit; macrophage inflammatory proteins; peptide chemical synthesis; protein engineering; synthetic protein; vaccine development

DESCRIPTION: (Adapted from applicant's abstract) This application focuses on the development of a novel strategy for designing and delivery of peptide antigens for HIV vaccine. Specifically, it is proposed to develop new methodology for preparing and delivery of the ectodomain chemokine receptor mimetics as HIV vaccine candidate. The rationale for developing receptor mimetics as vaccine is based on the recent reports linking HIV infectivity, tropism, and AIDS progression to coreceptors which belong to the 7-transmembrane (TM), G protein-coupled receptor family and are activated by the chemokines. Reversible blockage of these coreceptors in vitro and individuals with homozygous defect in the coreceptor allele provide evidence of correlation of HIV resistance to HIV infection. It is hypothesized that vaccination with conformationally constrained peptidyl immunogens mimicking the extracellular surface ectodomain of these coreceptors may confer useful therapeutic or preventive intervention in HIV infectivity and AIDS progression. There are two major impediments in using these 7-TM coreceptors directly as immunogens for vaccination. These include their insolubility and low immunogenicity. The goals are to design and develop soluble mimetics of the extracellular domains of these 7-TM receptors as vaccination candidates, to verify and test the mimetics biochemically and structurally, and to develop a general strategy for immunization and delivery of the CC-R5 mimetics for eliciting high-titer antisera in small animals

描述：（改编自申请人的摘要）该申请重点 开发肽设计和递送的新策略 HIV疫苗的抗原。 具体来说，建议开发新的 胞外域趋化因子受体的制备和递送方法 模仿者作为艾滋病毒疫苗的候选者。 开发受体的理由 作为疫苗的模仿物是基于最近有关艾滋病毒感染性的报告， 向性和艾滋病进展到属于 7-跨膜 (TM)，G 蛋白偶联受体家族，由 趋化因子。 这些辅助受体在体外和体外的可逆阻断 辅助受体等位基因存在纯合缺陷的个体提供了证据 HIV 耐药性与 HIV 感染的相关性。 假设 模仿构象限制的肽基免疫原进行疫苗接种 这些辅助受体的细胞外表面胞外域可能赋予有用的 HIV 感染和艾滋病的治疗或预防干预 进展。 使用这些 7-TM 有两个主要障碍 辅助受体直接作为疫苗接种的免疫原。 这些包括他们的 不溶性和低免疫原性。 目标是设计和开发 这些 7-TM 受体胞外结构域的可溶性模拟物 疫苗接种候选者，以生物化学方式验证和测试模拟物， 并制定免疫接种总体战略 递送 CC-R5 模拟物以在小样本中引发高滴度抗血清 动物