INTERSUBTYPE RECOMBINANTS FOR POLYVALENT ANTI-HIV VACCINE

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。 生产用于HIV感染的有效疫苗仍然很困难，这主要是由于人群中HIV毒株的巨大多样性，这是由于病毒能够频繁突变并与其他毒株重组，并不断表达逃避最初宿主免疫应答的新包膜序列。 此外，天然的、可复制的候选疫苗或载体（和活病毒）通常在病毒表面上产生和表达env蛋白，其具有严重糖基化的“聚糖盾”，其防止宿主免疫系统识别关键表位。 到目前为止，所有的候选疫苗和试验都只涉及HIV或SIV的一个或两个包膜序列，它们通常来自克隆的env序列，并且这些诱导对env的不良免疫应答，env是负责感染细胞的主要分子。 事实上，很少有单克隆抗体被发现能中和野生型病毒中的env。 然而，我们在凯斯西储的合作者已经开发出一种新的基于酵母的克隆技术，可以将许多不同的env序列整合到SHIV中，并且他们已经产生了新的进化枝C SHIV用于在猕猴中进行测试。 我们已经开始了这个项目，并将在今年内获得这些新病毒传播性的体内数据。

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. Producing an effective vaccine for HIV infection remains difficult, largely due to the tremendous diversity of HIV strains in the population, which has resulted from the viruses ability to mutate frequently and recombine with other strains and continually express new envelope sequences that evade the initial host immune response. Furthermore, native, replication competent vaccine candidates or vectors (and live virus) usually generate and express env proteins on the surface of viruses with a heavily glycosylated "glycan shield" that prevents the host immune system from recognizing key epitopes. To date, all vaccine candidates and trials have involved only one or two envelope sequences of HIV or SIV, which are usually from a clonal env sequence, and these induce poor immune responses against env, the primary molecule responsible for infecting cells. In fact very few monoclonal antibodies have been discovered that neutralize env in wild type viruses. However, our collaborators at Case Western Reserve have developed a new, yeast-based cloning technique that can incorporate numerous different env sequences in a SHIV and they have produced new clade C SHIVs for testing in macaques. We have started this project and will have in vivo data on the transmissibility of these new viruses within this year.