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

描述(申请人提供)：莱姆病是美国最流行的媒介传播疾病，疾控中心每年报告约30,000例，现已覆盖24个州。莱姆病的早期诊断和治疗对于防止疾病发展为以慢性关节炎、心脏炎或神经系统疾病为特征的系统性感染非常重要。如果患者并不是真的患有莱姆病，准确的阴性测试结果将有助于迅速指导医生寻找其他病因，并有望将不必要的抗生素治疗降至最低。目前还没有适合医生办公室使用的莱姆快速检测方法，目前基于实验室的两级莱姆检测算法(ELISA后Western印迹)存在成本高、结果产生时间慢(2-5天)、主观解释和对早期感染的低敏感性等问题。因此，S迫切需要一种性能更好的快速莱姆诊断测试。拟议项目的总体目标是开发和临床验证莱姆病的快速护理点检测，这将首次使任何医生的办公室都能获得准确的莱姆检测。在第一阶段，我们开发了一种莱姆快速检测原型，总周转时间为15分钟，在早期和晚期感染中表现出99%的特异性和敏感性，等于或高于FDA批准的ELISA检测。特别是，莱姆C6/C10快速检测对非常早期的莱姆感染(游走性红斑皮疹发病后1周)提供了很高的检测灵敏度，明显好于几种FDA批准的莱姆ELISA检测。快速莱姆检测基于三个创新组件：1)具有相当于ELISA的灵敏度的新型检测化学；2)C6和C10合成肽抗原的组合，对早期感染产生高灵敏度；以及3)一种免疫分析形式，克服了以前快速检测敏感抗体的限制。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，以便在医生的办公室环境中将其用作CLIA免检。在前瞻性和回溯性临床研究中，快速测试的性能将与目前的两级莱姆测试算法进行比较，以支持510(K)提交FDA批准。基于我们期望在这些研究中证明的高灵敏度和高特异度，我们将建议FDA声称莱姆快速检测可以替代两级方案中的一个或两个步骤。莱姆C6/C10快速检测将是我们新的快速检测技术的首次商业实施，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.