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DESIGN AND DELIVERY OF HIV CORECEPTOR BASED VACCINE

基于 HIV 受体的疫苗的设计和交付

基本信息

批准号：
6151208
负责人：
JAMES P TAM
金额：
$ 28.31万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-02-01 至 2002-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6151208
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

项目摘要

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：（改编自申请人摘要）本申请侧重于开发一种新的策略来设计和递送肽 HIV疫苗的抗原。具体而言，建议开发新的制备和递送胞外域趋化因子受体的方法作为HIV疫苗候选物的模拟物。开发受体的基本原理模拟物作为疫苗是基于最近的报告，向性，和艾滋病的进展，共受体属于 7-跨膜（TM），G蛋白偶联受体家族，并被激活，趋化因子这些辅助受体在体外的可逆阻断，辅助受体等位基因纯合缺陷的个体提供了证据，艾滋病病毒耐药性与艾滋病病毒感染的相关性。它是假设用构象受限的肽基免疫原模拟这些辅助受体的细胞外表面胞外域可以赋予有用的艾滋病毒传染性和艾滋病的治疗或预防干预进展在使用这些7-TM时有两个主要障碍辅助受体直接作为疫苗接种的免疫原。其中包括他们的免疫原性低。目标是设计和开发这些7-TM受体的胞外结构域的可溶性模拟物，疫苗接种候选人，以验证和测试模拟物的生物化学和在结构上，并制定一项全面的免疫战略，递送CC-R5模拟物以在小细胞中引发高滴度抗血清动物