An Inhalation Model of Q Fever in Guinea Pigs

豚鼠 Q 热吸入模型

• 批准号: 6797970
• 负责人: KASI E RUSSELL-LODRIGUE
• 金额: $ 11.3万
• 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 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6797970
• 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热是一种具有世界意义的人畜共患疾病，由专性细胞内细菌伯氏柯克斯体引起。由于伯内特念珠菌的高度传染性、其通过气溶胶感染的正常途径以及其在不利环境条件下的耐受性，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中。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，也没有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并不完整，并且尚未报道将该模型应用于疫苗测试。 拟议研究的具体目标是：1) 建立 Q 热豚鼠模型中的气溶胶感染途径，2) 表征气溶胶感染豚鼠的免疫反应，以及 3) 确定由气溶胶感染所赋予的保护性免疫的性质。重组蛋白。豚鼠将在一个专门设计的室中感染多剂量的伯内特念珠菌，该室旨在将液滴核直接输送到肺泡空间。将评估每只动物的临床体征、病理变化和对感染的免疫反应，并将其与剂量相关联。基于这些结果的单一致病剂量将用于疫苗攻击研究。这些研究的结果对于实现为有感染伯氏念珠菌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。 拟议的工作将为当前和未来的疫苗开发研究提供有关这种未充分利用的模型的重要信息，并使拉塞尔博士有机会作为独立研究者发展她的科学职业生涯。