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

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 我们实现了以下研究目标： 使用我们在前一个资助期间开发的第二个基于MJ4的系统，我们直接克隆了C亚型env基因的试点小组，这些基因是与Eric Hunter博士合作使用单基因组扩增(SGA)协议产生的。 在完成了40个C亚型HIV分子克隆的构建，代表了来自Susan Allen博士的赞比亚不和谐夫妇队列中3对匹配的供受者夫妇的病毒变体，并对C型HIV分子克隆在原代CD4T细胞上进行了复制分析后，我们通过计算曲线下面积(AUC)来定义复制表型，从而分析了每个分子克隆的复制动力学。 将我们在之前预算期间开发的Lac可调节双表达型腺病毒系统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伽马逆转录病毒-异嗜性小鼠白血病相关病毒(XMRV)的免疫原性。 意义：提供独特而有价值的试剂，是了解与艾滋病毒-1传播相关的表型的关键，以及有效预防艾滋病毒-1感染的疫苗的目标。

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.