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: 8172714
• 负责人: Marie-Claire Elisabeth Gauduin
• 金额: $ 34.22万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172714
• 关键词: Address; Adjuvant; Antigens; Cells; Computer Retrieval of Information on Scientific Projects Database; Data; Dermal; Development; Epithelial; Epithelial Cells; Funding; Goals; Grant; HIV; HIV Infections; HIV vaccine; Immune response; Immune system; Immunity; Infection; Institution; Life; Macaca mulatta; Mucosal Immune Responses; Mucous Membrane; Research; Research Personnel; 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; 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. 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 SIV疫苗研究产生的大量数据导致了以下建议：HIV疫苗是可以实现的。粘膜组织中的体液和细胞免疫反应在病毒传播的初始阶段阻塞或包含复制的能力可能对接种宿主抵抗感染的能力产生深远的影响。在粘膜入口门户上限制病毒复制的有效疫苗的开发可能是我们控制艾滋病毒感染的最大希望。我们认为，成功的疫苗有两个必要的特征：1）用病毒抗原对免疫系统的终生刺激； 2）艾滋病毒原发性复制部位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稳固的长期保护。为了满足这些要求，我们提出了一种替代方法，以成功将疫苗接种到粘膜部位并引起保护性粘膜免疫反应。我们建议将上皮干细胞用作病毒抗原的永久来源及其分化的后代作为产生抗原的呈现细胞。因此，目标是：1）研究将仅在终末分化的上皮细胞中表达的最佳启动子； 2）从恒河类细胞特异性启动子中引起SIV抗原的表达，该猕猴在由皮肤，阴道和直肠途径接种的恒河猕猴中。