CREATING ANTIBODIES TO ENABLE THE STUDY OF MYCOBACTERIUM TUBERCULOSIS INFECTIONS IN GUINEA PIGS

创造抗体以研究豚鼠结核分枝杆菌感染

• 批准号: 10027950
• 负责人: RON ORLANDO
• 金额: $ 65.32万
• 依托单位: GLYCOSCIENTIFIC, LLC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2021-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10027950
• 关键词: Address; Animal Model; Antibodies; Autopsy; Binding; Biological Markers; Cavia; Communicable Diseases; Development; Diagnosis; Disease; Effectiveness; Health; Human; IL2 gene; IL4 gene; IL6 gene; Immunologic Markers; Immunologics; Infection; JAK1 gene; Modeling; Modification; Monitor; Monoclonal Antibodies; Mus; Pathology; Phosphorylation; Positioning Attribute; Proteins; Reagent; Research; Research Personnel; STAT1 gene; STAT2 gene; STAT3 gene; Signal Transduction; Site; TNF gene; Tuberculosis; cross reactivity; epidemiology study; extracellular; mortality; next generation; nonhuman primate; phase 1 study; polyclonal antibody; response; tool; transmission process

Tuberculosis is a persistent infectious disease that threatens the health of people and numerous mammalian species throughout the world. Monitoring of Mycobacterium tuberculosis (Mtb) infections in animal models has often relied on host mortality, bacterial loads, and qualitative assessment of pathology at necropsy. These are blunt tools, largely unrelated to the markers used for diagnosis and epidemiological studies of human TB. The next generation of modeling requires matching the model and analysis to the specific research questions being asked. The lack of immunological reagents in most animal models severely limits our ability to address these questions through biomarker assessment in models more relevant than the mouse yet less expensive than non-human primates. We propose to generate reagents needed to elucidate and correlate immunological markers of tuberculosis (TB) transmission and disease development in the guinea pig. Thus, assessing tuberculosis disease stages in a relevant small mammalian model with the aid of crucial immunological reagents will greatly aid efforts into ultimately enhancing the effectiveness of current TB control efforts including a better understanding basic TB disease parameters in naturally infected mammalian models.

结核病是一种持续性传染病，威胁着世界各地人类和众多哺乳动物的健康。在动物模型中监测结核分枝杆菌(Mtb)感染通常依赖于宿主死亡率、细菌载量和尸检时的病理定性评估。这些都是迟钝的工具，与用于人类结核病诊断和流行病学研究的标记物基本无关。下一代建模需要将模型和分析与所提出的特定研究问题相匹配。在大多数动物模型中缺乏免疫试剂严重限制了我们通过在比小鼠更相关但比非人类灵长类动物更便宜的模型中进行生物标记物评估来解决这些问题的能力。我们建议生产所需的试剂来阐明和关联结核病(TB)在豚鼠中的传播和疾病发展的免疫标记物。因此，在关键免疫试剂的帮助下评估相关小型哺乳动物模型中的结核病疾病阶段将大大有助于最终加强当前结核病控制工作的有效性，包括更好地了解自然感染哺乳动物模型中的基本结核病疾病参数。