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EVASION OF ANTIGEN PRESENTATION BY RHESUS CYTOMEGALOVIRUS

EVASION OF ANTIGEN PRESENTATION BY RHESUS CYTOMEGALOVIRUS
恒河猴巨细胞病毒逃避抗原呈递
批准号:
8357750
负责人:
Klaus J Fruh
金额:
$9.74万
依托单位国家:
美国
项目类别:
财政年份:
2011
资助国家:
美国
项目状态:
已结题
起止时间:
2011-05-01 至 2012-04-30

项目摘要

项目成果

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中文摘要
翻译
该子项目是利用资源的许多研究子项目之一 由NIH/NCRR资助的中心赠款提供。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, 包括其他NIH来源。 列出的子项目总成本可能 表示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。 CMV疫苗开发的主要挑战之一是,尽管存在显著的抗体和T细胞应答,但CMV在CMV免疫个体中建立继发性持续感染。我们最近证明,CMV的超感染是由病毒US 2 -11糖蛋白-US 2,US 3,US 6和US 11-实现的,所有这些糖蛋白都抑制主要组织相容性复合物I类(MHC-I)向CD 8 + T细胞的抗原呈递。这些观察结果表明,缺乏US 2 -11区域的CMV可用于监测CMV特异性CD 8 + T细胞应答是否是“保护性的”,即,能够控制血清阳性个体所观察到的原发性病毒血症。因此,本提案的目标是定义针对US 2 -11缺失病毒的保护所需的CD 8 + T细胞应答,并将这些结果与针对野生型病毒的初次感染的保护相关联。另一个目标是确定US 2 -11区域中编码的每个单独的免疫消失素在促进超感染中的贡献。这项工作将挑战现有的范例,特别是假设活CMV疫苗需要基于复制CMV和单亚单位疫苗赋予保护性T细胞反应。我们还期望开发新的和改进的方法来测试CMV疫苗和改进基于CMV的载体。因此,我们相信我们的研究将对CMV疫苗和基于CMV的疫苗载体的开发产生重大而持久的影响。
英文摘要
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. One of the major challenges for CMV vaccine development is the fact that CMV establishes secondary persistent infections in CMV-immune individuals despite the presence of significant antibody and T cell responses. We recently demonstrated that super-infection by CMV is enabled by the viral US2-11 glycoproteins -US2, US3, US6 and US11- all of which inhibit antigen presentation by major histocompatibility complex class I (MHC-I) to CD8+ T cells. These observations suggest that CMV lacking the US2-11 region can be used to monitor whether a CMV-specific CD8+ T cell response is "protective", i.e., able to control primary viremia as observed for sero-positive individuals. A goal of this proposal is therefore to define the CD8+ T cell response required for protection against US2-11-deleted virus and to correlate these results with protection against primary infection with wildtype virus. A further goal is to determine the contribution of each individual immunevasin encoded in the US2-11 region in promoting super-infection. This work will challenge existing paradigms, specifically the assumptions that live CMV vaccines need to be based on replicating CMV and that single subunit vaccines confer protective T cell responses. We further anticipate to develop new and improved ways to test CMV vaccines and to improve CMV-based vectors. Therefore, we believe that our research will have a significant and lasting impact on the development of CMV vaccines and CMV-based vaccine vectors.
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