Poxviruses: Defining Epitope Immunodominance

痘病毒：定义表位免疫优势

• 批准号: 7698540
• 负责人: Masanori Terajima
• 金额: $ 41.08万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-15 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7698540
• 关键词: Adverse effects; Agammaglobulinemia; Antigen-Presenting Cells; Antigens; Bacteria; Binding; Biological Assay; CD8B1 gene; Cells; Cellular Immunity; DNA; Data; Development; Epitopes; Genes; HLA A*0201 antigen; Histocompatibility Antigens Class I; Human; Immune response; Immunization; Incidence; Infection; Licensing; Localized; Mammalian Cell; Methods; Peptide Library; Peptides; Polymerase Chain Reaction; Poxviridae; Proteins; Recovery; Relative (related person); Research Project Grants; Screening procedure; Smallpox; Smallpox Vaccine; Smallpox Viruses; Staging; System; T memory cell; T-Lymphocyte; T-Lymphocyte Epitopes; Transfection; Transgenic Mice; Vaccination; Vaccines; Vaccinia; Vaccinia virus; Viral Proteins; Virus; base; cross reactivity; cytotoxicity; design; enzyme linked immunospot assay; experimental analysis; neutralizing antibody; novel; prevent; response; synthetic peptide

Immunization with vaccinia virus resulted in long-lasting protection against smallpox and was the approach used to eliminate natural smallpox infections worldwide. This was accomplished without a detailed understanding of human T cell responses to poxviruses. Due to concerns about the use of smallpox virus as a bioweapon, smallpox vaccination is currently being reintroduced. Considering the relatively high incidence of side effects, developing a safer, but effective vaccine is very important. Vaccinia virus elicits strong cellular as well as humoral immune responses. Cellular immunity seems to be more important for recovery from infection. Severe complications from vaccination were associated with congenital or acquired T cell deficiencies, but not with congenital agammaglobulinemia. The presence of neutralizing antibody alone did not prevent the development of progressive vaccinia if cell-mediated immunity was defective. In order to analyze human T cell responses to licensed and experimental smallpox vaccines at the single cell level, it is essential to identify T cell epitopes, especially immunodominant CD8 ¿ T cell epitopes. Vaccinia is a large virus and we hypothesize that we can develop a rapid approach to localize gene fragments encoding human T cell epitopes and to identify them precisely using peptides using PCRgenerated DNA fragments containing virus genes transfected into antigen presenting cells. Complementary strategies will employ peptide libraries and studies in transgenic mice expressing common human MHC class I molecules. The immunodominance of human T cell epitopes on vaccinia virus will be analyzed. The results of this research project will provide valuable information relative to basic studies of human T cell memory and data useful for the design and analyses of experimental smallpox vaccines. The methods we will establish in this project may be applicable to other large viruses as well as bacteria for the definition of human T cell epitopes.

接种痘苗病毒可对天花产生持久的保护，是 用于消除世界各地自然天花感染的方法。这是在没有详细说明的情况下完成的 了解人类T细胞对痘病毒的反应。由于对使用天花病毒作为 目前正在重新引入生物武器和天花疫苗接种。考虑到发病率相对较高 在副作用方面，开发一种更安全但有效的疫苗是非常重要的。 痘苗病毒可引起较强的细胞免疫和体液免疫反应。细胞免疫似乎 对于从感染中恢复来说更重要。接种疫苗的严重并发症与 有先天性或获得性T细胞缺陷，但没有先天性无丙种球蛋白血症。他的存在 如果细胞介导，单靠中和抗体并不能阻止进行性牛痘的发展 豁免权是有缺陷的。为了分析人类T细胞对许可的和实验性的天花的反应 在单细胞水平上，识别T细胞表位，特别是免疫优势CD8T细胞是至关重要的 细胞表位。 牛痘是一种大病毒，我们假设我们可以开发出一种快速定位基因的方法。 编码人类T细胞表位的片段及其利用多肽精确鉴定的研究 含有病毒基因的DNA片段被导入抗原提呈细胞。互补性 策略将利用多肽库和在表达常见人类MHC的转基因小鼠中的研究 I类分子。将分析人类T细胞表位对痘苗病毒的免疫优势。这个 该研究项目的成果将为人类T细胞的基础研究提供有价值的信息 对设计和分析实验天花疫苗有用的记忆和数据。我们的方法是 将在本项目中建立可能适用于其他大型病毒以及细菌的定义 人类T细胞表位。