This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Rickettsia prowazekii is the causative agent of epidemic typhus, a vector (louse)-borne disease characterized by a sudden onset of febrile symptoms with significant pathologic sequelae. In addition to causing epidemic disease in poor and unhygienic environments, R. prowazekii has also been identified as possessing the characteristics of a biological weapon. There presently is no vaccine available for protection against epidemic typhus, although development of new products is currently underway. A fully characterized primate model of disease is needed to determine immune response, safety, and protective efficacy of vaccine products developed to protect against R. prowazekii infection. The goal of this project is to develop a robust nonhuman model of disease for epidemic typhus in order to accelerate testing of newly developed vaccine products. The specific hypothesis is that use of the Rhesus macaque (Macaca mulatta) of Chinese origin will provide an optimal test system for an infection model of epidemic typhus. We base this hypothesis upon the observations from limited past studies that detailed 1) a clear dose-response relationship in prior model development efforts with the Breinl strain using Rhesus macaques when directly compared to experimental infection with avirulent strains, and 2) typical pathology in the form of disseminated vasculitis including typhus nodules in the central nervous system that emulated the human clinical syndrome. Based on these observations, the experimental focus of this proposal is on the model development of epidemic typhus in the Rhesus macaque.
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