DETERMINANTS OF IMMUNOLOGIC RESPONSIVENESS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。我们的主要目的是研究宿主基因的变异性，预测对吸附炭疽疫苗（AVA）的抗体应答和不良反应的变异性。进入AVA 000队列代表了探索影响疫苗应答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，突出HLA和非HLA遗传因子在宿主对疫苗的反应中的作用。研究领域1（RA 1）将主要集中在正在进行的试验中的炭疽疫苗接种者。我们将选择被认为可能影响疫苗结果的基因，鉴定这些基因中的遗传变异，并寻找多态性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（RA 2）涉及两个子项目，一个是AVA疫苗接种者，另一个是健康对照。在这两个子项目中，为了确定遗传变异与试验参与者反应的有希望的关联是否实际上反映了遗传决定的蛋白质表达和功能差异，我们将表征与B细胞增殖、生理学、表面标志物表达和抗体产生相关的基因中变异的功能意义。由于该项目的性质和复杂性，我们与各个领导人定义了三个不同的子项目。子项目可能在不同的时间开始开始，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.