An Inhalation Model of Q Fever in Guinea Pigs

描述（由申请人提供）：Q热是一种世界性的人畜共患疾病，由专性胞内细菌伯纳克希菌引起。由于伯纳蒂胞杆菌的高传染性、其通过气溶胶的正常感染途径以及其在恶劣环境条件下的耐受性，该生物已被列入可能用于生物恐怖主义和生物战的病原体名单。用于研究这种疾病的动物模型包括通过腹腔接种感染的小鼠和豚鼠。很少有研究利用气溶胶感染，也没有研究评估吸入剂量对临床疾病的影响。关于豚鼠对Q热的免疫反应的描述是不完整的，并且该模型在疫苗测试中的应用尚未报道。

DESCRIPTION (provided by applicant): Q fever is a zoonotic disease of worldwide significance caused by the obligate intracellular bacterium Coxiella burnetii. Due to the highly infectious nature of C. burnetii, its normal route of infection by aerosol, and its hardiness in adverse environmental conditions, the organism has been included in the list likely agents to be used in bioterrorism and biological warfare. Animal models being used to study this disease include mice and guinea pigs infected through intraperitoneal inoculation. Few studies have utilized aerosol infection, and none have evaluated the effect of inhalation dose on clinical disease. Descriptions of the immune response in guinea pigs to Q fever are incomplete, and application of this model for vaccine testing has not been reported. The specific aims for the proposed studies are: 1) Establish the aerosol route of infection in the guinea pig model of Q fever, 2) Characterize the immune response in aerosol-infected guinea pigs, and 3) Determine the nature of protective immunity conferred by recombinant proteins. Guinea pigs will be infected with multiple doses of C.burnetii in a specialized chamber designed to deliver droplet nuclei directly to the alveolar spaces. Each animal's clinical signs, pathologic changes, and immunologic response to infection will be evaluated and correlated with dose. A single disease-causing dose based on these results will be used in vaccine challenge studies. The findings of these studies are of utmost importance in reaching the long-range goal of the development of a safe, effective subunit vaccine for individuals at risk of infection with C. burnetii. The proposed work will provide vital information about this underutilized model for use in current and future vaccine development studies and will allow Dr. Russell the opportunity to develop her scientific career as an independent investigator.