EPITHELIAL CELLS AS MUCOSAL ADJUVANT FOR LIFE LONG IMMUNITY

上皮细胞作为终身免疫的粘膜佐剂

• 批准号: 8357687
• 负责人: Marie-Claire Elisabeth Gauduin
• 金额: $ 34.1万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357687
• 关键词: Address; Adjuvant; Antigens; Cells; Data; Dermal; Development; Epithelial; Epithelial Cells; Funding; Goals; Grant; HIV; HIV Infections; HIV vaccine; Immune response; Immune system; Immunity; Infection; Life; Macaca mulatta; Mucosal Immune Responses; Mucous Membrane; National Center for Research Resources; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Route; SIV; SIV Vaccines; Site; Solid; Source; Staging; Stem cells; Suggestion; United States National Institutes of Health; Vaccinated; Vaccines; Vagina; Viral; Viral Antigens; Virus; cost; keratinocyte; mucosal site; offspring; promoter; rectal; transmission process

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. 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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 SIV 疫苗研究产生的大量数据表明 HIV 疫苗是可以实现的。在病毒传播的初始阶段，粘膜组织中的体液和细胞免疫反应阻断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产生深远的影响。开发一种有效的疫苗来限制病毒在粘膜入口的复制可能是我们控制艾滋病毒感染的最佳希望。我们认为成功的疫苗有两个必要特征：1）病毒抗原对免疫系统的终生刺激； 2) HIV 初级复制位点的靶向免疫反应。同时解决这两个问题的疫苗方法将有可能实现可靠、长期的保护。为了满足这些要求，我们提出了一种替代方法来成功地将疫苗递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，并将其分化的后代作为产生抗原的呈递细胞。因此，我们的目标是： 1）研究专门在终末分化上皮细胞中表达的最佳启动子； 2) 在通过皮肤、阴道和直肠途径接种疫苗的恒河猴中，从终末分化的角质形成细胞特异性启动子中引发SIV抗原表达。