EPITHELIAL CELLS AS MUCOSAL ADJUVANT FOR LIFE LONG IMMUNITY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 SIV疫苗研究产生的大量数据导致了艾滋病毒疫苗是可以实现的。在病毒传播的初始阶段，粘膜组织中体液和细胞免疫反应阻止或遏制复制的能力可能对接种疫苗的宿主抵抗感染的能力有深远的影响。开发一种有效的疫苗，限制病毒在进入粘膜的入口复制，可能是我们控制艾滋病毒感染的最大希望。我们认为，一种成功的疫苗有两个必要的特征：1)用病毒抗原终身刺激免疫系统；2)在艾滋病毒的初级复制部位进行有针对性的免疫反应。同时解决这两个问题的疫苗方法将有可能实现坚实的长期保护。为了满足这些要求，我们提出了一种替代方法，成功地将疫苗输送到粘膜部位，并引发保护性粘膜免疫反应。我们建议使用上皮干细胞作为病毒抗原的永久来源，并将其分化的后代用作产生抗原的呈递细胞。因此，我们的目标是：1)研究在终末分化的上皮细胞中唯一表达的最佳启动子；2)通过经皮、阴道和直肠途径免疫恒河猴，诱导终末分化的角质形成细胞特异性启动子表达SIV抗原。

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. The significant amount of data generated by SIV vaccine studies has led to the suggestion that an HIV vaccine is achievable. The capacity of humoral and cellular immune responses in mucosal tissues to block or contain replication at the initial stage of virus transmission may have a profound impact on the ability of a vaccinated host to resist infection. The development of an effective vaccine that restricts viral replication at the mucosal portal of entry may be our best hope for controlling HIV infection. We believe there are two necessary features for a successful vaccine: 1) life-long stimulation of the immune system with viral antigens; and 2) a targeted immune response at the site of primary replication of HIV. A vaccine approach that simultaneously addresses these two issues would have the potential to achieve solid, long-term protection. To fulfill these requirements, we propose an alternative approach to successfully deliver a vaccine to mucosal sites and elicit protective mucosal immune responses. We propose to use the epithelial stem cell as a permanent source of viral antigen and their differentiated offspring as antigen producing presenting cells. Therefore, the goal is: 1) To investigate the best promoter that will be expressed exclusively in terminally differentiated epithelial cells; and, 2) To elicit SIV antigen expression from a terminally differentiated keratinocyte-specific promoter in rhesus macaques vaccinated by dermal, vaginal and rectal routes.