Application of Novel Antigens and Integrated Microfluidics for Leprosy Diagnosis

描述（由申请人提供）：本申请的总体目标是开发一种特定和简单的诊断测试，以识别麻风分枝杆菌感染的个体，从而持续发现新病例，使麻风的合理化学预防不仅可以减少感染负担，还可以减少神经损伤和残疾。我们假设这样的诊断测试可以通过测量患者和接触者外周血样本中对特定麻风分枝杆菌抗原的免疫反应模式来实现。该提案的具体目标是：1)利用先进的生物信息学开发一种特异性和简单的第一代诊断测试，以识别麻风分枝杆菌特异性肽，这些肽预计将与11个主要HLA-DR等位基因结合，并激活t细胞释放IFN-，并将其纳入QuantiFERON(R)平台；2)鉴定新的麻风分枝杆菌抗原，包括糖蛋白和脂糖蛋白，在感染期间触发先天和获得性免疫反应；3)开发一种先进的集成微流控便携式诊断测试，同时测量多种免疫参数，提高特异性、敏感性，并可能预测疾病。拟议的实验战略将确保开发一种便携式、最先进的诊断测试，以发现麻风分枝杆菌感染，确定持续新病例的来源，而且还将开发一种新的技术平台，可以很容易地适应在麻风流行地区和其他被忽视的热带传染病实施。麻风病仍然是发展中国家的一个主要卫生和经济负担。我们建议开发一种基于微流体的便携式诊断测试，以诊断感染和持续传播源，允许知情的化学预防，从而进一步减少全球麻风病负担，包括疾病并发症，包括对皮肤、神经、四肢和眼睛的永久性损伤。

DESCRIPTION (provided by applicant): The overall objective of this application is to develop a specific and simple diagnostic test to identify individuals infected with Mycobacterium leprae and therefore sources of continuing new case detection, enabling rational chemoprophylaxis of leprosy leading not only to decrease in infectious burden but in reductions in nerve damage and disabilities. We hypothesize that such a diagnostic test can be achieved by measuring the immunologic response patterns to specific M. leprae antigens in peripheral blood samples from patients and contacts. The specific aims of this proposal are to: 1) develop a specific and simple first generation diagnostic test using advanced bioinformatics to identify M. leprae-specific peptides predicted to bind to 11 major HLA-DR alleles and to activate T-cell release of IFN-, to be incorporated into the QuantiFERON(R) platform; 2) To identify novel M. leprae antigens, including glycoproteins and lipoglycoproteins, that trigger innate and acquired immune responses during infection; and, 3) to develop an advanced integrated microfluidics-based portable diagnostic test to simultaneously measure multiple immunologic parameters providing enhanced specificity, sensitivity, and, perhaps, predictions of disease. The proposed experimental strategy will ensure development of a portable, state-of-the-art diagnostic test to detect M. leprae infection, identify sources of continuing new cases but also a new technology platform that can be readily adapted to implementation in leprosy endemic areas and to other neglected tropical infectious diseases. H Leprosy continues as a major health and economic burden in developing countries. We propose to develop a microfluidics-based portable diagnostic test to allow diagnosis of infection and sources of continuing transmission, allowing informed chemoprophylaxis and thereby further reduction in the global leprosy burden including disease complications including permanent damage to the skin, nerves, limbs and eyes.