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.

通过离甲酸病毒免疫可产生对天花的持久保护，是 用于消除全球天然天花感染的方法。这是没有详细的 了解人类T细胞对痘病毒的反应。由于担心使用天花病毒作为 目前正在重新引入生物武器，天花疫苗接种。考虑到相对高事件 副作用，开发更安全但有效的疫苗非常重要。 离子病毒会引起强细胞和体液免疫调查。细胞免疫喜欢 对于从感染中恢复更为重要。疫苗接种的严重并发症是相关的 先天性或获得的T细胞缺陷，但没有先天性agammagamaglobloblobloinemia。存在 如果细胞介导 免疫力有缺陷。为了分析人类T细胞对许可和实验天花的反应 在单细胞水平上的疫苗，必须鉴定T细胞表位，尤其是免疫主导CD8€t 细胞表位。 疫苗是一种大型病毒，我们假设我们可以开发一种快速的方法来定位基因 编码人T细胞表位的片段，并使用Pcrgenated使用肽精确识别它们 含有病毒基因的DNA片段转化为抗原呈现细胞。补充 策略将在表达常见人MHC的转基因小鼠中采用肽库和研究 I类分子。将分析人类T细胞表位对离子病毒病毒的免疫优势。 该研究项目的结果将提供有关人类T细胞基础研究的宝贵信息 记忆和数据可用于实验天花疫苗的设计和分析。我们的方法 该项目将在此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。