VACCINE-INDUCED CD8+ T CELL MEMORY

疫苗诱导的 CD8 T 细胞记忆

• 批准号: 8173257
• 负责人: MARK K SLIFKA
• 金额: $ 7.61万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 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/8173257
• 关键词: Antiviral Agents; Biological Models; CD8B1 gene; Chronic; Computer Retrieval of Information on Scientific Projects Database; Data; Formaldehyde; Funding; Grant; Heating; Hydrogen Peroxide; Infection; Institution; Interferons; Interleukin-2; Life; Lymphocytic choriomeningitis virus; Mus; Peptides; Production; Proliferating; Proteins; Research; Research Personnel; Resources; Source; Structure; T cell response; T memory cell; T-Lymphocyte; TNF gene; Techniques; United States National Institutes of Health; Vaccination; Vaccines; Virion; Virus; Virus Diseases; crosslink; cytokine; in vivo; novel strategies; vaccine development

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 In these studies, we present unpublished new data demonstrating a novel approach to vaccine development in which we inactivate intact virus particles using hydrogen peroxide (H202).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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 在这些研究中，我们提供了未发表的新数据，证明了一种新的疫苗开发方法，其中我们使用过氧化氢 (H2O2) 灭活完整的病毒颗粒。 这种方法比传统方法更好地保留了病毒颗粒/蛋白质的抗原结构 其他常用的灭活技术，例如热、甲醛或紫外线交联。 测定是否有过氧化氢 由于疫苗可能能够诱导有效的 T 细胞记忆，因此我们使用 LCMV（淋巴细胞脉络膜脑膜炎病毒）作为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，接种 H2O2 灭活的 LCMV 会诱导易于检测的病毒特异性 CD8+ T 细胞反应，该反应是多功能的，能够产生细胞因子（IFN、TNF 和 IL-2）以及针对肽的体内 CTL 活性- 涂层靶材。 此外，我们还证明，接受该疫苗的小鼠能够产生病毒特异性 CD8+ T 细胞，这些细胞在活病毒攻击后迅速增殖，并能够清除慢性 LCMV 克隆 13 感染，这表明该疫苗引发的抗病毒 T 细胞反应对慢性病毒感染有保护作用。