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异性和简单的诊断测试，以识别麻风分枝杆菌感染的个体，从而持续检测新病例的来源，从而实现麻风病的合理化学预防，不仅减少感染负担，而且减少神经损伤和残疾。我们推测，这种诊断试验可以通过测量对特定M的免疫应答模式来实现。病人和接触者外周血样本中的麻风抗原。本提案的具体目标是：1）利用先进的生物信息学技术开发一种特异而简单的第一代诊断试验来鉴定M。预测麻风特异性肽与11个主要HLA-DR等位基因结合并激活IFN-γ的T细胞释放，将其掺入QuantiFERON平台; 2）鉴定新的M.麻风抗原，包括糖蛋白和脂糖蛋白，其在感染期间触发先天性和获得性免疫应答;以及，3）开发先进的基于集成微流体的便携式诊断测试，以同时测量多个免疫学参数，从而提供增强的特异性、灵敏度以及可能的疾病预测。拟议的实验策略将确保开发一种便携式，最先进的诊断测试，以检测M。该项目不仅可用于麻风病感染，还可查明持续新发病例的来源，而且是一个新的技术平台，可随时适用于麻风病流行地区和其他被忽视的热带传染病。H麻风病仍然是发展中国家的一个主要健康和经济负担。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的来源，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.