HIV-1 VACCINE CANDIDATES USING NEWLY TRANSMITTED CLADE C ENVS AS IMMUNOGENS

使用新传播的 C 型 ENVS 作为免疫原的 HIV-1 候选疫苗

• 批准号: 8172411
• 负责人: Jerry L Blackwell
• 金额: $ 5.48万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172411
• 关键词: Antibody Formation; Antigens; Area Under Curve; Biological; Biological Assay; CCR5 gene; CD4 Positive T Lymphocytes; Characteristics; Coculture Techniques; Collaborations; Computer Retrieval of Information on Scientific Projects Database; Couples; Dendritic Cells; Development; Evaluation; Event; Funding; Genetic; Genome; Glycoproteins; Goals; Grant; HIV; HIV-1; Infection; Institution; Kinetics; Laboratories; Methods; Molecular Cloning; Phenotype; Protocols documentation; Reagent; Research; Research Personnel; Resources; Screening procedure; Source; System; United States National Institutes of Health; Vaccines; Variant; Viral; base; cohort; design; env Genes; fitness; immunogenicity; neutralizing antibody; transmission process; vaccine candidate

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project was designed to evaluate the protective immunogenicity of HIV-1 Envelope (Env) glycoproteins cloned from newly transmitted clade C infections. Based on conserved biological and genetic characteristics we hypothesized that the transmitted Env would induce cross-protective neutralizing antibody responses. We achieved the following research goals during 2008: + Using the the second MJ4-based system that we developed in the previous funding period, we directly cloned a pilot panel of subtype C env genes that were generated in collaboration with Dr. Eric Hunter using a Single-Genome Amplication (SGA) protocol. Development of such a system will provide for our laboratory as well as that of other researchers a relatively high through-put and robust method for screening the a wide array of HIV-1 env genes. + After completing the construction of 40 subtype C HIV molecular clones representing the viral variants from 3 matched Donor/Recipient couples from Dr. Susan Allen's Zambian discordant couple cohort and performing replication assays on the subtype C HIV molecular clones on primary CD4 T cells, we have now analyzed the he replication kinetics of each molecular clone by calculating the Area Under the Curve (AUC) to define the replication phenotype. Our primary observation shows that replication fitness is not the only characteristic associated with the Donor-to-Recipient transmission event. + Completed our evaluation of the replication kinetics of the subtype C HIV molecular clones on primary CD4 T cells and CD4 T cell-dendritic cell co-cultures and following treatment to increase CCR5 expression. Our results indicated that there was no significant increase in replication kinetics due to co-culture conditions or CCR5 expression levels. The significance of this progress is that it provides unique and valuable reagents that are key to understanding the phenotype associated with HIV-1 transmission and the targets for an effective vaccine for protection from HIV-1 infection.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该项目旨在评估从新传播的进化枝C感染中克隆的HIV-1包膜（ENV）糖蛋白的保护性免疫原性。 基于保守的生物学和遗传特征，我们假设传输的ENV将诱导交叉保护中和抗体反应。我们在2008年实现了以下研究目标： +使用我们在上一个融资期间开发的第二个基于MJ4的系统，我们直接克隆了使用单基因组放大（SGA）协议与Eric Hunter博士合作生成的亚型C ENV基因的试验小组。这种系统的开发将为我们的实验室以及其他研究人员提供一种相对较高的通行和强大方法，用于筛选各种HIV-1 Env基因。 +在完成了40个亚型的hiv分子克隆构造后，代表了来自3个匹配的供体/接受者的病毒变异，来自苏珊·艾伦（Susan Allen）博士的赞比亚不矛盾夫妇夫妇队列中的夫妇群​​体，并在主要的CD4 T细胞上对亚型的cliber clive calcare clive car clire clational carnicals进行分析，并在亚型中进行复制测定，并在亚型中进行复制。 （AUC）定义复制表型。我们的主要观察结果表明，复制适应性并不是与供体到接收器事件相关的唯一特征。 +完成了我们对原代CD4 T细胞和CD4 T细胞树枝状细胞共培养的亚型C HIV分子克隆复制动力学的评估，并在治疗后以增加CCR5表达。 我们的结果表明，由于共培养条件或CCR5表达水平，复制动力学没有显着增加。 这种进度的意义在于，它提供了独特而有价值的试剂，这是了解与HIV-1传播相关的表型的关键，以及用于保护HIV-1感染的有效疫苗的靶标。