Antibody Biomarkers for Early Detection of Tuberculosis

用于结核病早期检测的抗体生物标志物

基本信息

批准号：
8319299
负责人：
D MITCHELL MAGEE
金额：
$ 36.2万
依托单位：
ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-15 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8319299
关键词：
Acid Fast Bacillae Staining Method Antibodies Antibody Formation Antigens Bacillus (bacterium)Biological Assay Biological Markers Biosensor Blinded Care Technology Points Categories Control Groups Country Couples Cross-Sectional Studies DNA Data Data Analyses Detection Developing Countries Development Devices Diagnosis Diagnostic Diagnostic Procedure Diagnostic tests Disease Disease Progression Early Diagnosis Electronics Environment Enzyme-Linked Immunosorbent Assay Exhibits Foundations Genome Genomics Geographic Locations Goals Gold HIV Immunoassay Immunocompetent Immunoglobulin A Immunoglobulin G Immunoglobulin M Immunological Diagnosis Incidence Infection Interferon Type II International Lead Lung diseases Measures Microscopic Multidrug-Resistant Tuberculosis Mycobacterium tuberculosis Mycobacterium tuberculosis antigens National Institute of Allergy and Infectious Disease Nucleic Acids Patient Care Patients Performance Persons Population Pregnancy Tests Printing Production Protein Array Protein Microchips Proteins Proteome Proteomics Public Health Reaction Time Recombinants Reporting Reproducibility Resources Sampling Screening procedure Sensitivity and Specificity Serologic tests Serological Serum Set protein Signs and Symptoms South Africa Sputum Staging Technology Testing Thoracic Radiography Tuberculosis Validation base cost cost effective experience gene cloning improved novel novel diagnostics nucleic acid detection pathogen point of care programs prototype response success tool transmission process validation studies

项目摘要

DESCRIPTION (provided by applicant): Mycobacterium tuberculosis (Mtb), an NIAID Category C agent, infects approximately one-third of the world's population, and an estimated 9.4 million people develop active tuberculosis (TB) each year. The poor detection rate of TB cases, especially in developing countries, promotes this level of ongoing transmission. In resource-poor regions, direct microscopic examination of sputum smears for acid fast bacilli (AFB) provides the prime diagnostic tool. The AFB smear test exhibits poor sensitivity at approximately ~50% in immunocompetent persons, and is even less sensitive in HIV+ TB+ patients. In order to interrupt this cycle of infection-transmission, we need improvements in rapid diagnostic capabilities, independent of Mtb-specific nucleic acid detection, for difficult to diagnose patients like those co-infected HIV. Towards that end, these proposed studies will demonstrate that detection of antibody biomarkers produced in response to active TB would add a powerful adjunct to the current diagnostic armamentarium. To accomplish this, we will obtain sera from well-defined patient and control groups, and screen these sera on a unique and novel platform, nucleic acid programmable protein arrays (NAPPA), which allows for display of the complete proteome of Mtb on a microarray. The screen of a complete representative proteome using patient and control sera will allow us to delineate a smaller set of target proteins which we will validate using an acquired set of independent samples obtained in cross-sectional studies of TB suspects. The results of the validation study will yield a select set of ~30 candidate proteins that could serve to detect antibody biomarkers in TB patients. We will then test these in Enzyme-Linked-Immunosorbent Assays (ELISA) to validate the data acquired in the microarray studies and to provide prototyping of a diagnostic. The antigen-antibody interaction provides the foundation for many diagnostics, which will allow transferring these discoveries into a commonly used point-of-care technology platform, such as the "dipstick" style test, or into emerging electronic biosensor platforms. Our goal is to find and delineate the most sensitive and specific Mtb proteins that react with patient antibodies. Our assembled team couples the expertise of both TB patient care and diagnosis with high throughput genomics, proteomics, and antibody screening to accelerate progress on this ancient disease. The successful completion of this program will provide new and improved strategies for detecting TB rapidly and sensitively, in formats that can be applied in all settings globally.

描述（由申请人提供）：结核分枝杆菌 (Mtb) 是一种 NIAID C 类病原体，感染世界上大约三分之一的人口，估计每年有 940 万人患上活动性结核病 (TB)。结核病病例的检出率很低，尤其是在发展中国家，这促进了这种持续传播的水平。在资源贫乏地区，直接用显微镜检查痰涂片中的抗酸杆菌 (AFB) 是主要的诊断工具。 AFB 涂片测试在免疫功能正常的人中表现出较差的敏感性，约为 50%，对于 HIV+ TB+ 患者的敏感性甚至更低。为了中断这种感染传播循环，我们需要提高快速诊断能力，独立于结核分枝杆菌特异性核酸检测，以诊断难以诊断的患者，例如那些同时感染艾滋病毒的患者。为此，这些拟议的研究将证明，对活动性结核病产生的抗体生物标志物的检测将为当前的诊断装备增添强大的辅助手段。为了实现这一目标，我们将从明确的患者和对照组中获取血清，并在独特且新颖的平台——核酸可编程蛋白质阵列（NAPPA）上筛选这些血清，该平台可以在微阵列上显示结核分枝杆菌的完整蛋白质组。使用患者和对照血清筛选完整的代表性蛋白质组将使我们能够描绘出一组较小的目标蛋白质，我们将使用在结核病嫌疑人的横断面研究中获得的一组独立样本进行验证。验证研究的结果将产生一组精选的约 30 种候选蛋白质，可用于检测结核病患者的抗体生物标志物。然后，我们将在酶联免疫吸附测定 (ELISA) 中测试这些数据，以验证微阵列研究中获得的数据并提供诊断原型。抗原-抗体相互作用为许多诊断奠定了基础，这将允许将这些发现转移到常用的护理点技术平台（例如“试纸”式测试）或新兴的电子生物传感器平台中。我们的目标是找到并描述与患者抗体发生反应的最敏感和最特异的 Mtb 蛋白。我们的团队将结核病患者护理和诊断的专业知识与高通量基因组学、蛋白质组学和抗体筛选相结合，以加速这一古老疾病的进展。该计划的成功完成将为快速、灵敏地检测结核病提供新的和改进的策略，其格式可适用于全球所有环境。