CruziScreen, a recombinant antigen-based screening test for Chagas disease

CruziScreen，一种基于重组抗原的恰加斯病筛查测试

• 批准号: 9407719
• 负责人: DARRICK Albert CARTER
• 金额: $ 15.74万
• 依托单位: PAI LIFE SCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9407719
• 关键词: Annual Reports; Antibodies; Antigens; Binding; Blood; Blood Screening; Canis familiaris; Central America; Cessation of life; Chagas Disease; Chimeric Proteins; Chronic; Country; Data; Detection; Development; Diagnostic; Diagnostic tests; Disease; Enzyme-Linked Immunosorbent Assay; Epitopes; Evaluation; Generations; Goals; Health Care Costs; Immigration; Individual; Infection; Inflammatory; Insecta; Laboratories; Lead; Mass Screening; Nature; Organ; Parasites; Phase; Polyproteins; Prevention; Process; Production; Proteins; Reagent; Recombinants; Reference Standards; Research; Risk; Sampling; Sensitivity and Specificity; Serological; Serum; South America; Syndrome; System; Tandem Repeat Sequences; Testing; Trypanosoma cruzi; United States; United States Food and Drug Administration; base; commercialization; cost effective; diagnostic screening; fight against; global health; improved; large scale production; novel; novel diagnostics; programs; prototype; response; screening; tool; transmission process; uptake; vector

Project Summary Chagas disease is a severe inflammatory syndrome caused by infection with a protozoan parasite, Trypanosoma cruzi. Although transmission occurs mostly through an intermediate insect host, the infection is silent and chronic carriers pose a significant risk through the transfer of infected products made from donated blood of these individuals to blood recipients. Up to 500,000 new cases and 66,000 deaths are reported annually in countries in South and Central America where the parasite lives. The combination of immigration and expansion of the range where the parasite host lives is, however, leading to large numbers of infected individuals in countries that until recently did not have Chagas disease. The United States is foremost amongst these. Control and prevention of Chagas disease relies on the accurate detection of infection. Improvements in the currently available diagnostics are required. In our research we have found a novel way to identify pieces of the parasite (certain proteins) that could be used as components of a new diagnostic test. Since they have the ability to tightly bind antibodies from infected individuals and are often selected from a variety of individual diagnostic leads, we stitch them together as “multiple antibody-binding epitopes” to enhance the diagnostic power. These “polyproteins” maximize the ability to react with infected serum, enabling the new test. We have used computational searches to identify a number of novel diagnostic candidates in T. cruzi and our preliminary data indicate several that hold promise as important components with a new diagnostic test. The research in this proposal will develop an improved and cost- effective diagnostic test to permit screening for T. cruzi infection / Chagas disease. The proposed research will proceed in two steps: In step 1 we will optimize and tightly define the production parameters of two lead polyproteins. In step 2 we will integrate these diagnostic leads into a format consistent with use in standard reference laboratories/ blood centers as well distribute them to our extensive network of collaborators in a wide variety of T. cruzi-endemic regions for further evaluation. If successful, in the phase II application, prototype tests and adjunct test formats will be produced and extensively evaluated as potential commercial tests.

项目摘要 恰加斯病是一种严重的炎症综合征，由原生动物感染引起 克氏锥虫虽然传播主要是通过一种中间昆虫 宿主，感染是沉默的，慢性携带者通过转移 受感染的产品由这些人捐献给受血者的血液制成。最高50万 南美洲和中美洲国家每年报告新病例和66，000例死亡 寄生虫生活的地方移民和扩大的范围相结合， 然而，寄生虫宿主的生活正在导致大量受感染的个人在国家， 直到最近都没有查加斯病。美国是其中的佼佼者。控制 而恰加斯病的预防依赖于对感染的准确检测。改善 需要当前可用的诊断。 在我们的研究中，我们发现了一种新的方法来识别寄生虫的片段（某些蛋白质）， 可以作为新的诊断测试的组成部分。因为它们有能力将 抗体来自感染的个体，并且通常选自各种个体诊断抗体。 线索，我们将它们缝合在一起作为“多个抗体结合表位”，以增强诊断 动力.这些“多蛋白”最大限度地提高了与感染血清反应的能力， test.我们已经使用计算搜索来确定一些新的诊断候选人 于T. cruzi和我们的初步数据表明，有几个有希望作为重要组成部分 新的诊断测试该研究将开发一种改进的和成本- 有效的诊断测试，以允许筛选T。克氏锥虫病 拟议的研究将分两步进行：在步骤1中，我们将优化并严格定义 两种铅多聚蛋白的生产参数。在第2步中，我们将整合这些诊断线索 转换成与标准参考实验室/血液中心一致的格式 将它们分发给我们广泛的合作者网络。克鲁西特有的 区域进行进一步评估。如果成功，在第二阶段的应用，原型测试和辅助 将制作测试格式，并作为潜在的商业测试进行广泛评估。