Application of Novel Antigens and Integrated Microfluidics for Leprosy Diagnosis

新型抗原和集成微流控技术在麻风病诊断中的应用

• 批准号: 7940892
• 负责人: ROBERT L MODLIN
• 金额: $ 34.65万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-28 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7940892
• 关键词: Address; Alleles; Antibodies; Antibody Formation; Antigens; Area; Arts; Bacillus (bacterium); Bacteria; Bacteriology; Binding; Biochemical; Bioinformatics; Biological Assay; Blood specimen; CD4 Positive T Lymphocytes; Characteristics; Chemoprophylaxis; Classification; Clinical; Communicable Diseases; Contracts; Control Groups; Detection; Developing Countries; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Progression; Early Diagnosis; Economic Burden; Ensure; Epidemiology; Epitopes; Eye; Focal Infection; Frequencies; Funding; Generations; Genetic; Glycolipids; Glycopeptides; Glycoproteins; Goals; HLA-DR Antigens; Histocompatibility Antigens Class II; Human; Humoral Immunities; Immune; Immune response; Immunologics; Immunology; Incidence; Individual; Infection; Interferons; Interleukin-10; Interleukin-4; Interleukin-5; Invaded; Investigation; Laboratories; Lepromatous Leprosy; Leprosy; Lesion; Limb structure; Lipoprotein (a); Measures; Microbe; Microfluidics; Molecular Biology; Morphology; Mycobacterium leprae; National Institute of Allergy and Infectious Disease; Nerve; Neurologic Deficit; Outcome; Patients; Pattern; Peptides; Population; Progressive Disease; Protein Glycosylation; Proteins; Public Health; Recombinants; Research Personnel; Resources; Risk; Screening procedure; Sensitivity and Specificity; Serum; Skin; Source; Staging; T cell response; T-Lymphocyte; Technology; Testing; Toll-like receptors; Tropical Disease; Tuberculoid leprosy; Tuberculosis; United States National Institutes of Health; base; cell mediated immune response; chemotherapy; cytokine; disability; disease classification; disorder prevention; fundamental research; health economics; high risk; improved; insight; light microscopy; meetings; microbial; neglect; new technology; novel; novel diagnostics; pathogen; peripheral blood; portability; prevent; response; skin lesion; transmission process

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.

描述(由申请人提供)：本申请的总体目标是开发一种特殊和简单的诊断测试，以确定感染麻风杆菌的个人，从而确定持续新病例检测的来源，使麻风能够合理地进行化学预防，不仅减少感染负担，而且减少神经损伤和残疾。我们假设，这种诊断试验可以通过测量患者和接触者外周血样本中特定麻风杆菌抗原的免疫反应模式来实现。这项建议的具体目的是：1)利用先进的生物信息学开发一种特异而简单的第一代诊断测试方法，以确定预计将与11个主要HLA-DR等位基因结合的麻风杆菌特异性多肽，并激活T细胞释放干扰素，将其整合到Quantiferon(R)平台中；2)识别新型麻风杆菌抗原，包括糖蛋白和脂糖蛋白，可在感染期间触发先天性和获得性免疫反应；以及3)开发一种先进的基于微流控技术的便携式综合诊断测试方法，以同时测量多个免疫学参数，从而提高特异性、敏感性，甚至可能还能预测疾病。拟议的实验战略将确保开发一种便携的、最先进的诊断测试，以检测麻风杆菌感染，查明持续新病例的来源，并确保建立一个新的技术平台，以便随时适应麻风病流行地区和其他被忽视的热带传染病的实施。H麻风病仍然是发展中国家的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，从而进行知情的化学预防，从而进一步减少全球麻风负担，包括疾病并发症，包括皮肤、神经、四肢和眼睛的永久性损害。