A NONHUMAN PRIMATE MODEL OF RICKETTSIA PROWAZEKII INFECTION (EPIDEMIC TYPHUS)

普瓦泽克立克次体感染（流行性斑疹伤寒）的非人类灵长类动物模型

• 批准号: 7562382
• 负责人: CHAD J. ROY
• 金额: $ 3.04万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7562382
• 关键词: Biological; Characteristics; Chinese People; Clinical; Computer Retrieval of Information on Scientific Projects Database; Development; Disease; Disease model; Dose; Environment; Epidemic; Fever; Funding; Goals; Grant; Human; Immune response; Infection; Institution; Lice; Macaca mulatta; Modeling; Neuraxis; Nodule; Pathologic; Pathology; Primates; Research; Research Personnel; Resources; Rickettsia prowazekii; Safety; Source; Symptoms; Syndrome; System; Testing; Typhus; United States National Institutes of Health; Vaccines; Vasculitis; base; model development; nonhuman primate; response; vaccine efficacy; vector

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. Rickettsia prowazekii is the causative agent of epidemic typhus, a vector (louse)-borne disease characterized by a sudden onset of febrile symptoms with significant pathologic sequelae. In addition to causing epidemic disease in poor and unhygienic environments, R. prowazekii has also been identified as possessing the characteristics of a biological weapon. There presently is no vaccine available for protection against epidemic typhus, although development of new products is currently underway. A fully characterized primate model of disease is needed to determine immune response, safety, and protective efficacy of vaccine products developed to protect against R. prowazekii infection. The goal of this project is to develop a robust nonhuman model of disease for epidemic typhus in order to accelerate testing of newly developed vaccine products. The specific hypothesis is that use of the Rhesus macaque (Macaca mulatta) of Chinese origin will provide an optimal test system for an infection model of epidemic typhus. We base this hypothesis upon the observations from limited past studies that detailed 1) a clear dose-response relationship in prior model development efforts with the Breinl strain using Rhesus macaques when directly compared to experimental infection with avirulent strains, and 2) typical pathology in the form of disseminated vasculitis including typhus nodules in the central nervous system that emulated the human clinical syndrome. Based on these observations, the experimental focus of this proposal is on the model development of epidemic typhus in the Rhesus macaque.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 普氏立克次体是流行性斑疹伤寒的病原体，流行性斑疹伤寒是一种媒介（虱子）传播的疾病，其特征是突然出现发热症状并伴有明显的病理学后遗症。 除了在恶劣和不卫生的环境中引起流行病外，R。prowazekii也被确定具有生物武器的特征。 目前还没有预防流行性斑疹伤寒的疫苗，尽管新产品的开发正在进行中。 需要一种完全表征的灵长类动物疾病模型来确定用于预防R.普氏感染 该项目的目标是开发一个强大的非人类流行性斑疹伤寒疾病模型，以加速新开发的疫苗产品的测试。 具体的假设是，使用恒河猴（Macaca mulatta）的中国起源将提供一个最佳的测试系统的流行性斑疹伤寒的感染模型。 我们将这一假设建立在来自有限的过去研究的观察结果的基础上，这些研究详细描述了1）当直接与无毒力菌株的实验感染进行比较时，在使用恒河猴的Breinl菌株的先前模型开发工作中存在明确的剂量-反应关系，以及2）以播散性血管炎形式存在的典型病理学，包括中枢神经系统中模仿人类临床综合征的斑疹伤寒结节。 基于这些观察结果，本建议的实验重点是在恒河猴中流行性斑疹伤寒的模型开发。