Vaccination and infection: indicators of immunological health and responsiveness

描述(申请人提供)：在这项提案中，我们的目标是使用系统生物学方法来调查一系列不同疫苗的免疫反应性，包括季节性和新大流行H1N1v、带状疱疹、麻疹和脑膜炎奈瑟氏菌。在流感和带状疱疹的情况下，我们也将能够直接将疫苗的免疫反应与对病原体本身的自然反应进行比较。这些调查将比较不同的年龄组-儿童、年轻人和老年人-以寻找免疫能力的特定标记物和分析，特别是那些可能在不同病原体和年龄组中通用的标记物和分析。我们还将调查免疫系统受损或失调的个体对流感疫苗的反应，以了解这些反应可能如何偏离健康个体。我们将采用一种简化的模型，在该模型中，来自接触不同疫苗或传染病的个人的临床样本都将在我们的人类免疫监测中心进行一系列基本免疫功能的分析，并进行几种“最先进”的分析，例如我们最近开发的高通量人类白细胞抗原测序技术，它能够同时生成数百人的完整人类白细胞抗原单倍型。我们还将进行选定的免疫球蛋白和T细胞受体谱系分析以及组合肽-MHC四聚体分析，以有效地搜索信息丰富的T细胞表位。我们将采用先进的生物信息学分析，例如我们新的细胞类型特定SAM算法(CsSAM)，它使用细胞子集信息从全血基因表达数据中获得更高的灵敏度，并开发新的生物信息学工具，以询问我们所有项目、试点和核心的丰富和复杂的数据库。

DESCRIPTION (provided by applicant): In this proposal, we aim to use a systems biology approach to survey immune responsiveness across a range of different vaccines including influenza, both seasonal and the new pandemic H1N1v, Herpes zoster, Measles, and the bacterium Neisseria meningitidis. In the case of influenza and Herpes zoster, we will also be able to directly compare the immune response to vaccines with those natural responses to the pathogen itself. These investigations will compare different age groups-children, young adults, and the elderly-to look for specific markers and assays of immune competence and especially those that might be common across different pathogens and age groups. We will also survey the influenza vaccine responses of individuals with impaired or dysregulated immune systems in order to see how these might deviate from healthy individuals. We will employ a streamlined model in which clinical specimens from individuals exposed to different vaccines or infectious diseases will all be assayed for an array of basic immune functions in our Human Immune Monitoring Center and also for several "state of the art" assays such as our recently developed high throughput HLA sequencing technique, which is able to generate complete HLA haplotypes from hundreds of people simultaneously. We will also perform selected Immunoglobulin and T Cell Receptor repertoire analysis and combinatorial peptide-MHC tetramer analysis to efficiently search for informative T cell epitopes. We will employ advanced bioinformatics analysis such as our new cell type specific SAM algorithms (csSAM), which use cell subset information to achieve much higher sensitivity from whole blood gene expression data as well as developing new bioinformatics tools to interrogate our rich and complex data base across all projects, pilots and cores.