VACCINATION AGAINST INTRAPARTUM HIV-L CLADE C TRANSMISSION SUPPLEMENT

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 我们与Dana Farber癌症研究所合作，正在使用HIV感染和艾滋病的恒河猴模型来开发针对HIV Clade C株（HIV-C）的潜在疫苗策略，这是世界上最流行的毒株。补助金补充专门寻求确定保护的相关性，在接种疫苗的恒河猴与长寿的抗病毒免疫。对于潜在疫苗的有效性测试，我们已经开发了一系列的杂交病毒，（SHIV）通过结合猴免疫缺陷病毒的遗传成分与包膜基因直接从赞比亚儿童样本克隆。然后使SHIV适应恒河猴，产生能够通过粘膜途径诱导感染并维持病毒载量和疾病的攻击储备物以测试疫苗功效。令人感兴趣的是，SHIV 1157 ipd 3的Env是从一个新生儿中分离出来的，尽管病毒载量高，但新生儿的CD 4水平仍保持了10年，而来自SHIV 2873 Nip的Env是从一个发展为AIDS并在9个月时死亡的新生儿中分离出来的，这表明Env是跨物种的致病决定因素。针对SHIV-C分离株的攻击，有目的地测试疫苗效力，所述分离株与疫苗抗原开发以模拟真实现场条件的分离株异源。我们还分析了这些动物中抗体反应的精细特异性，以确定能够在HIV毒株中诱导广泛交叉中和抗体的包膜的特定位点，这是新HIV疫苗的关键组成部分。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In association with the Dana Farber Cancer Institute, we are using the rhesus macaque model of HIV infection and AIDS to develop potential vaccine strategies against the Clade C strain of HIV (HIV-C) the world's most prevalent strain. The grant supplement specifically seeks to determine the correlates of protection in a vaccinated Rhesus with long-lived antiviral immunity. For efficacy testing of potential vaccines, we have developed a series of hybrid viruses, (SHIVs) by combining genetic components of simian immunodeficiency virus with envelope genes cloned directly from Zambian pediatric samples. SHIVs are then adapted to rhesus macaques generating challenge stocks capable of inducing infection via mucosal routes and sustaining viral loads and disease to test vaccine efficacy. Of interest is the fact that the Env of SHIV1157ipd3 was isolated from a newborn who has maintained high CD4 levels in spite of high viral loads for 10 years while Env from SHIV2873Nip was isolated from a newborn that developed AIDS and died at 9 months, suggesting Env as a pathogenic determinant across species. Vaccine efficacy is purposely tested against challenges with SHIV-C isolates that are heterogonous to the isolates from which the vaccine antigens are developed to mimic reality field conditions. We are also analyzing the fine-specificity of the antibody responses in these animals to identify specific sites of envelope able to induce broadly cross-neutralizing antibodies across HIV strains, a key component of new HIV vaccines.