DETERMINANTS OF IMMUNOLOGIC RESPONSIVENESS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。我们的中心目的是研究宿主基因的变异性，预测对炭疽吸附疫苗(AVA)的抗体反应和不良反应的变异。进入AVA000队列是探索影响疫苗反应的宿主因素的无与伦比的机会。它将扩展我们和其他人的工作，强调人类白细胞抗原和非人类白细胞抗原遗传因素在宿主对疫苗反应中的作用。在正在进行的试验中，研究区域1(RA1)将主要集中在炭疽疫苗接受者身上。我们将选择被认为可能影响疫苗结果的基因，识别这些基因中的遗传变异，并寻找多态与炭疽保护性抗原抗体水平和不良反应的关联。研究领域2(RA2)涉及两个子项目，一个是接种AVA疫苗的项目，另一个是健康对照项目。在这两个子项目中，为了确定基因变异与试验参与者的反应之间有希望的关联是否真的反映了基因决定的蛋白质表达和功能的差异，我们将表征与B细胞增殖、生理、表面标记表达和抗体产生相关的基因变异的功能意义。由于这个项目的性质和复杂性，我们定义了三个不同的子项目，每个领导人都有。子项目可能在不同的时间开始，但最终将同时进行。

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. Our central purpose is to investigate variability in host genes predicting variation in antibody responses and adverse reactions to Anthrax Vaccine Adsorbed (AVA). Access to the AVA000 cohort represents an unparalleled opportunity to explore host factors influencing vaccine responses. It will extend work by us and others highlighting the role of both HLA and non-HLA genetic factors in host responses to vaccines. Research Area 1 (RA1) will concentrate largely on anthrax vaccine recipients in the ongoing trial. We will select genes believed likely to influence vaccine outcomes, identify genetic variants in these genes, and search for associations of the polymorphisms with levels of antibody to anthrax protective antigen and with adverse reactions. Research Area 2 (RA2) involves two subprojects, one in the AVA vaccinees and one in the healthy controls. In these two subprojects, to determine whether the promising associations of genetic variations with responses of trial participants actually reflect genetically determined differences in protein expression and function, we will characterize the functional significance of variants in genes related to B cell proliferation, physiology, surface marker expression and antibody production. Because of the nature and complexity of this project, we have defined three distinct subprojects with individual leaders. The subprojects may begin at different times but will eventually proceed concurrently.