VACCINE-INDUCED CD8+ T CELL MEMORY

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。 在这些研究中，我们展示了一种未发表的新数据，证明了一种新的疫苗开发方法，在这种方法中，我们使用过氧化氢(H202)灭活完整的病毒颗粒。这种方法更好地保存了病毒颗粒/蛋白质的抗原性结构 其他常用的灭活技术，如加热、甲醛或UV交联法。以确定过氧化氢是否 疫苗可能能够诱导有效的T细胞记忆，我们使用LCMV(淋巴细胞性脉络膜脑膜炎病毒)作为一个严格的模型系统来表征疫苗诱导的T细胞反应。 我们已经证明，用过氧化氢灭活的LCMV接种可以诱导容易检测到的病毒特异性CD8+T细胞反应，这种反应是多功能的，能够产生细胞因子(干扰素、肿瘤坏死因子和IL-2)，以及体内针对多肽包裹的靶点的CTL活性。此外，我们还证明，接种该疫苗的小鼠能够产生病毒特异性CD8+T细胞，在活体病毒攻击后迅速增殖，并能够清除慢性LCMV克隆13感染，表明该疫苗诱导的抗病毒T细胞反应对慢性病毒感染具有保护作用。

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. In these studies, we present unpublished new data demonstrating a novel approach to vaccine development in which we inactivate intact virus particles using hydrogen peroxide (H202). This approach preserves the antigenic structure of virus particles/proteins better than other commonly used inactivation techniques such as heat, formaldehyde, or UV cross-linking. To determine if hydrogen peroxide vaccines might be capable of inducing effective T cell memory, we have used LCMV (lymphocytic choriomeningitis virus) as a rigorous model system for characterizing vaccine-induced T cell responses. We have demonstrated that vaccination with H2O2-inactivated LCMV induces a readily detectable virus-specific CD8+ T cell response that is multi-functional and capable of cytokine production (IFN, TNF, and IL-2) as well as in vivo CTL activity against peptide-coated targets. Moreover, we have demonstrated that mice that receive this vaccine are able to generate virus-specific CD8+ T cells that rapidly proliferate following live virus challenge and are able to clear chronic LCMV clone 13 infection, indicating that the antiviral T cell response elicited by this vaccine is protective against chronic viral infection.