ANTIBODY BASED DIAGNOSTIC FOR TB IN NONHUMAN PRIMATES

非人类灵长类动物结核病的抗体诊断

• 批准号: 2717408
• 负责人: Carol A. Nacy
• 金额: $ 10万
• 依托单位: SEQUELLA, INC.
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2717408
• 关键词: Macaca mulatta; Mycobacterium bovis; Mycobacterium tuberculosis; SDS polyacrylamide gel electrophoresis; antibacterial antibody; bacterial antigens; diagnosis design /evaluation; immunologic skin test; serology /serodiagnosis; tuberculin test; tuberculosis

Sequella will explore use of early-onset Ab produced by infection of rhesus monkeys with M. tb as a potential diagnostic for identifying or confirming absence of this disease in quarantined animals and nonhuman primate colonies. The current skin test reagent produces unacceptably high numbers of false negative and positive reactions. The purpose of this Phase I proposal is (a) to identify antigens of M. tb to which nonhuman primates (as opposed to humans) develop immunological reactivity, and (b) to determine the time course and immunoglobulin class of Ab produced to TB antigens in serum and in feces. The results of these studies will help select both the correct antigen(s) to detect early Ab and the type of Ab detection system (by Ab class) that will most appropriately form the basis of a new serologic or scatologic diagnostic. A successful Phase I study would stimulate a Phase II application to confirm Ab to the same or different antigens in M. bovis- infected rhesus monkeys, extend these observations to other nonhuman primates infected with the two etiologic agents of TB, identify the appropriate test format for highest sensitivity and specificity, and perform clinical trials to validate the serologic/scatologic diagnostic and compare it to the current skin test. PROPOSED COMMERCIAL APPLICATION: Sequella will develop a proprietary position with Mycos, Inc. on antigens that are specifically useful for the diagnosis of TB in nonhuman primates; Sequella will also patent any innovative technology it develops to detect Ab, (specifically anti-mycobacterial Ab) in serum or feces. Should a sensitive and specific diagnostic be the result of these studies, and the clinical evaluation suggests that this test is superior to the currently approved skin test, Sequella and its partners will seek approval of the diagnostic by the USDA as an adjunct or replacement for the skin test. With approval, Sequella and its partners will have such the diagnostic manufactured and marketed to interested veterinary groups, in private or public institutions.

Sequella将探索使用由感染猪瘟病毒产生的早发性抗体 携带结核分枝杆菌的恒河猴可能被诊断为 确认在被检疫的动物和非人类中没有这种疾病 灵长类动物群体。目前的皮肤测试试剂生产的产品令人无法接受 大量的假阴性和阳性反应。目的 这项第一阶段的建议是：(A)确定结核分枝杆菌的抗原 非人灵长类动物(与人类相对)产生免疫力 反应性，以及(B)测定时间进程和免疫球蛋白 在血清和粪便中产生的针对结核抗原的抗体类别。结果是 这些研究将有助于选择正确的抗原(S)进行检测 早期抗体和抗体检测系统的类型(按抗体类别) 最恰当地形成了新的血清学或血液学的基础 诊断。一项成功的第一阶段研究将刺激第二阶段 牛分枝杆菌抗同一或不同抗原抗体的确认应用 被感染的恒河猴，将这些观察扩展到其他非人类 被两种结核病病原体感染的灵长类动物，识别 适当的测试格式以获得最高的灵敏度和特异度，以及 进行临床试验以验证血清学/皮肤学诊断 并将其与目前的皮肤测试进行比较。 建议的商业应用： Sequella将与Mycos，Inc.在 对结核病的诊断特别有用的抗原 非人灵长类；Sequella还将为任何创新技术申请专利 发展到检测血清中的抗体(特别是抗分枝杆菌抗体) 或者粪便。如果敏感和特定的诊断结果是 这些研究和临床评估表明，这项测试是 优于目前批准的皮肤测试，Sequella及其合作伙伴 将寻求美国农业部批准诊断为附属或 皮肤测试的替代品。在获得批准后，Sequella及其合作伙伴 将制造这种诊断并将其销售给感兴趣的人 私人或公共机构中的兽医团体。