CHARACTERIZATION OF BRUCELLOSIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 布鲁氏菌病是一种慢性肉芽肿性感染，由细胞内细菌布鲁氏菌的几个亚型引起。美国每年有不到100例自然布鲁氏菌病，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)。布鲁氏菌病的人类疫苗还没有开发出来，一些在动物身上使用的成功的减毒活疫苗(LAV)仍然对人类具有致病性。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机制。在所有被评估的哺乳动物物种中，布鲁氏菌的致病性各不相同。小鼠和豚鼠模型的人类疫苗开发分别存在使用近交系菌株和结果的推广有限的缺点，以及用于彻底表征对疫苗的免疫反应的试剂的低可用性。非人灵长类动物(NHP)是临床前研究的首选动物模型，因为它们在生理和遗传学上比其他任何动物都更接近人类。NHP对布鲁氏菌强毒株或弱毒株的感染很敏感，最近的研究表明，感染布氏杆菌16M的恒河猴发生了与人类布鲁氏菌病相似的病理变化。该项目的近期目标是确定布氏杆菌病的恒河猴模型，并确定疾病进展和保护的潜在免疫标记物。

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.