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)本申请重点 关于设计和递送多肽的新策略的发展 HIV疫苗的抗原。具体地说，建议开发新的 胞外趋化因子受体的制备和递送方法 作为HIV疫苗候选的模拟物。发展受体的基本原理 作为疫苗的模拟物是基于最近关于艾滋病毒传染性的报道， 嗜性和艾滋病进展到属于 7-跨膜(TM)，G蛋白偶联受体家族，并由 趋化因子。体外可逆性阻断这些辅助受体和 辅受体等位基因纯合子缺陷个体提供证据 艾滋病毒抵抗力与艾滋病毒感染之间的相关性。据推测， 模拟构象限制性多肽免疫原的免疫接种 这些辅受体的胞外表面胞外结构域可能会提供有用的 艾滋病毒感染性和艾滋病的治疗性或预防性干预 进步。使用这些7-TM有两个主要障碍 辅受体直接作为免疫原用于疫苗接种。其中包括他们的 不溶性和低免疫原性。我们的目标是设计和开发 这些7-TM受体胞外结构域的可溶性模拟 候选疫苗接种，以验证和测试模拟生物化学和 在结构上，并制定免疫的一般战略和 CC-R5模拟物在小鼠体内诱导高效价抗血清的研究 动物