An Inhalation Model of Q Fever in Guinea Pigs

豚鼠 Q 热吸入模型

• 批准号: 6933944
• 负责人: KASI E RUSSELL-LODRIGUE
• 金额: $ 11.57万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6933944
• 关键词: Coxiella burnetii; Q fever; aerosols; bioterrorism /chemical warfare; disease /disorder model; guinea pigs; immunity; immunoregulation; model design /development; recombinant proteins; respiratory infections

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.

描述（由申请人提供）：Q热是由专性细胞内细菌伯内特（Coxiella burnetii）引起的全球意义的人畜共患病。由于C. burnetii的高度感染性，气溶胶的正常感染途径及其在不利环境条件下的坚韧性，该生物已包括在列表中，可能会用于生物恐怖主义和生物战。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。很少有研究利用气溶胶感染，没有人评估吸入剂量对临床疾病的影响。豚鼠对Q发烧中免疫反应的描述是不完整的，并且尚未报道该模型在疫苗测试中的应用。 拟议研究的具体目的是：1）在Q Fever的豚鼠模型中建立气溶胶感染途径，2）表征了感染了气雾剂的豚鼠中的免疫反应，3）确定由重组蛋白赋予的保护性免疫的性质。豚鼠将在一个专门的腔室中用多剂c.burnetii感染，旨在将液滴核直接传递到肺泡空间。将评估每种动物的临床体征，病理变化以及对感染的免疫学反应，并与剂量相关。基于这些结果的单一致病剂量将用于疫苗挑战研究。这些研究的发现对于达到开发有效，有效的亚基疫苗的远程目标至关重要，该疫苗是为患有C. burnetii感染风险的个体。 拟议的工作将提供有关这种未充分利用模型的重要信息，以用于当前和未来的疫苗开发研究，并使罗素博士有机会发展她作为独立研究者的科学生涯。