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

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。 为子项目列出的总成本可能 表示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。 我们实现了以下研究目标： + 使用我们在上一个资助期开发的第二个基于MJ 4的系统，我们直接克隆了一组与Eric Hunter博士合作使用单基因组扩增（SGA）方案产生的C亚型env基因的试验性小组。 + 在完成代表来自Susan艾伦博士的赞比亚不一致夫妇队列的3对匹配的供体/供体夫妇的病毒变体的40个亚型C HIV分子克隆的构建并在原代CD 4 T细胞上对亚型C HIV分子克隆进行复制测定后，我们现在通过计算曲线下面积（AUC）来分析每个分子克隆的复制动力学，以确定复制表型。 + 将我们在先前预算期间开发的Lac-regulatable dual expression adenovirus vector system应用于一个新的疫苗项目，在该项目中，我们正在研究最近发现的γ逆转录病毒、异嗜性小鼠白血病相关病毒（XMRV）的免疫原性。 重要性：提供独特和有价值的试剂，是了解与HIV-1传播相关的表型和有效抗HIV-1感染疫苗靶点的关键。

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. We achieved the following research goals: + Using 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. + 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. + Applied the Lac-regulatable dual expression adenovirus vector system that we developed during the previous budget periods to a new vaccine project where we are investigating the immunogenicity of the recently discovered gammaretrovirus, xenotropic murine leukemia-related virus (XMRV). Significance: Provides unique and valuable reagents, key to understanding the phenotype associated with HIV-1 transmission and the targets for an effective vaccine against HIV-1 infection.