Rapid point of care test for Lyme serodiagnosis based on novel ultra sensitive de

描述（由申请人提供）：莱姆病是美国最流行的媒介传播疾病，CDC每年报告的病例约为30，000例，范围现已覆盖24个州。莱姆病的早期诊断和治疗对于防止疾病进展为以慢性关节炎、心脏炎或神经系统疾病为特征的全身感染是重要的。如果患者没有真正患有莱姆病，准确的阴性检测结果将有助于及时指导医生寻找其他病因，并希望尽量减少不必要的抗生素治疗。没有适合医生办公室使用的莱姆病快速测试是商业上可获得的，并且目前基于实验室的双层莱姆病测试算法（ELISA，然后是蛋白质印迹）遭受高成本、获得结果的时间慢（2-5天）、主观解释和对早期感染的低灵敏度。因此，迫切需要具有改进性能的快速莱姆病诊断测试。拟议项目的总体目标是开发和临床验证莱姆病的快速即时检测，这将首次使任何医生办公室都能进行准确的莱姆病检测。在第一阶段，我们开发了一种总周转时间为15分钟的原型莱姆快速测试，其在早期和晚期感染中表现出>99%的特异性和灵敏度，等于或大于FDA批准的ELISA测试。特别地，莱姆C6/C10快速测试为非常早期的莱姆感染（游走性红斑皮疹发作后<1周）提供了高检测灵敏度，显著优于几种FDA批准的莱姆ELISA测试。快速莱姆病检测基于三个创新组件：1）具有ELISA等效灵敏度的新型检测化学，2）C6和C10合成肽抗原的组合，对早期感染具有高灵敏度，以及3）免疫测定形式，克服了快速检测灵敏抗体检测的先前限制。在第二阶段，我们将 优化和验证全血和血清/血浆样本的快速检测，使其能够在医生的办公室环境中用作CLIA豁免检测。在前瞻性和回顾性临床研究中，将快速检测的性能与当前的两级莱姆试验算法进行比较，以支持FDA批准的510（k）提交。基于我们期望在这些研究中证明的高灵敏度和特异性，我们将提出FDA声明，即莱姆快速试验可以替代双层方案的一个或两个步骤。莱姆病C6/C10快速检测将是我们新型快速检测技术的首次商业应用，并将首次实现准确的当天莱姆病诊断结果，这可能导致莱姆病检测标准方案的基本范式转变。

DESCRIPTION (provided by applicant): Lyme disease is the most prevalent vector-borne disease in the U.S., with about 30,000 cases per year reported by CDC and a range now covering 24 states. Early diagnosis and treatment of Lyme disease is important to prevent the disease from progressing to a systemic infection characterized by chronic arthritis, carditis or neurological disorders. Where a patient does not truly have Lyme disease, an accurate negative test result would be valuable in promptly directing a physician to seek other causes of illness and hopefully minimize unnecessary antibiotic therapy. No Lyme rapid test suitable for physician's office use is commercially available, and the current laboratory-based two-tier Lyme testing algorithm (ELISA followed by Western blot) suffers from high cost, slow time to results (2-5 days), subjective interpretation and low sensitivity for early infections. Accordingly, there s a critical need for a rapid Lyme diagnostic test with improved performance. The overall objective of the proposed project is the development and clinical validation of a rapid, point-of-care test for Lyme disease that will for the first time make accurate Lyme testing accessible to any physician's office. In Phase I we have developed a prototype Lyme rapid test with 15 minute total turnaround time, which exhibited >99% specificity and sensitivity equal to or greater than that of FDA-cleared ELISA tests in both early and late stage infections. In particular, the Lyme C6/C10 rapid test provided high detection sensitivity for very early Lyme infections (<1 week post-onset of erythema migrans rash), significantly better than several FDA- cleared Lyme ELISA tests. The rapid Lyme test is based on three innovative components: 1) novel detection chemistry with ELISA-equivalent sensitivity, 2) a combination of C6 and C10 synthetic peptide antigens yielding high sensitivity for early infections, and 3) an immunoassay format that overcomes previous limitations of rapid tests for sensitive antibody detection. In Phase II we will optimize and validate the rapid test for both whole blood and serum/plasma samples, to enable its use as a CLIA-waived test in a physician's office environment. Performance of the rapid test will be compared to that of the current two-tier Lyme testing algorithm in prospective and retrospective clinical studies to support a 510(k) submission for FDA clearance. Based on the high sensitivity and specificity which we expect to demonstrate in these studies, we will propose an FDA claim that the Lyme rapid test may substitute for one or both steps of the two-tier protocol. The Lyme C6/C10 rapid test will be the first commercial implementation of our novel rapid test technology, and will, for the first time, enable accurate, same-day Lyme disease diagnostic results which could lead to a basic paradigm shift in the standard protocol for Lyme testing.