An Inhalation Model of Q Fever in Guinea Pigs

描述（由申请方提供）：Q热是一种由专性细胞内细菌贝氏柯克斯体引起的具有全球意义的人畜共患疾病。由于C.由于贝氏体、其通过气溶胶的正常感染途径以及其在不利环境条件下的抵抗力，该生物体已被列入可能用于生物恐怖主义和生物战的制剂清单。用于研究这种疾病的动物模型包括通过腹膜内接种感染的小鼠和豚鼠。很少有研究利用气雾剂感染，没有一个评价吸入剂量对临床疾病的影响。关于豚鼠对Q热的免疫应答的描述尚不完整，并且尚未报道该模型在疫苗试验中的应用。 拟定研究的具体目的是：1）在Q热豚鼠模型中建立气溶胶感染途径，2）表征气溶胶感染豚鼠的免疫应答，3）确定重组蛋白赋予的保护性免疫的性质。豚鼠将在专门设计用于将液滴核直接递送至肺泡腔的专门腔室中感染多剂量的贝氏隐孢子虫。将评价每只动物的临床体征、病理学变化和对感染的免疫反应，并与剂量相关。基于这些结果的单次致病剂量将用于疫苗攻毒研究。这些研究的结果对于实现为有感染C的风险的个体开发安全、有效的亚单位疫苗的长期目标至关重要。伯内特氏菌 拟议的工作将提供关于这种未充分利用的模型的重要信息，用于当前和未来的疫苗开发研究，并将使Russell博士有机会发展她作为独立研究者的科学事业。

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.