CHARACTERIZATION OF BRUCELLOSIS

布鲁氏菌病的特征

• 批准号: 8172720
• 负责人: Jean L. Patterson
• 金额: $ 17.27万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172720
• 关键词: Affect; Animal Model; Animals; Attenuated; Attenuated Live Virus Vaccine; Bacteria; Brucella; Brucella melitensis; Brucellosis; California; Categories; Cavia; Chronic; Computer Retrieval of Information on Scientific Projects Database; Disadvantaged; Disease Progression; Funding; Genetic; Goals; Grant; Granulomatous; Human; Immune; Immune response; Immunologic Markers; Inbred Strain; Infection; Institution; Macaca mulatta; Modeling; Mus; National Institute of Allergy and Infectious Disease; Organism; Pathogenicity; Pathologic; Physiology; Reagent; Research; Research Personnel; Resources; Source; Texas; United States National Institutes of Health; Vaccines; Virulent; nonhuman primate; pathogen; pre-clinical research; transmission process; vaccine development; weapons

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Brucellosis is a chronic granulomatous infection caused by several subtypes of the intracellular bacteria Brucella. There are less than 100 cases/year of natural brucellosis in USA, which occur predominantly in California and Texas; however, due to the possibility of airborne transmission of this pathogen, Brucella is considered a potential biologic weapon (NIAID category B agent). A human vaccine has not been developed for brucellosis, and some of the successful live-attenuated vaccines (LAV) used in animals still retain pathogenicity for humans. A major difficulty affecting the development of a vaccine against human brucellosis is the absence of well-established immune correlates of protection. Pathogenicity varies among Brucella species in all mammalian species evaluated. The mouse and guinea pig model of human vaccine development have the disadvantage of using inbred strains and consequent limited generalization of the results, and low availability of reagents for a thorough characterization of the immune response to the vaccines, respectively. Nonhuman primates (NHP) are the preferred animal models for pre-clinical research because they approximate humans in physiology and genetics more closely than any other animal. NHP are susceptible to infection with virulent or attenuated strains of Brucella organisms, and recent studies have shown that rhesus macaques infected with B. melitensis 16 M develop pathologic changes similar to the ones observed in human brucellosis. The immediate goal of this project is to define the rhesus macaque model for brucellosis and to identify potential immune markers of disease progression and protection.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 布鲁氏菌病是由细胞内布鲁氏菌的几种亚型引起的慢性肉芽肿感染。 美国每年自然布鲁氏菌病病例不到 100 例，主要发生在加利福尼亚州和德克萨斯州；然而，由于这种病原体可能通过空气传播，布鲁氏菌被认为是一种潜在的生物武器（NIAID B 类制剂）。 目前尚未开发出针对布鲁氏菌病的人类疫苗，一些成功用于动物的减毒活疫苗（LAV）仍然保留对人类的致病性。 影响人类布鲁氏菌病疫苗开发的一个主要困难是缺乏完善的免疫相关保护。 在所有评估的哺乳动物物种中，布鲁氏菌属物种的致病性各不相同。人类疫苗开发的小鼠和豚鼠模型的缺点是使用近交系，因此结果的推广有限，并且用于全面表征疫苗免疫反应的试剂可用性较低。 非人灵长类动物（NHP）是临床前研究的首选动物模型，因为它们在生理学和遗传学上比任何其他动物更接近人类。 NHP 很容易受到布鲁氏菌强毒株或减毒株的感染，最近的研究表明，感染 B. melitensis 16 M 的恒河猴会出现与人类布鲁氏菌病中观察到的病理变化相似的病理变化。 该项目的近期目标是定义布鲁氏菌病的恒河猴模型，并确定疾病进展和保护的潜在免疫标志物。