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.
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