Multiplex Microarray for Tuberculosis

描述（由申请人提供）：在世界范围内，结核病造成的人类死亡人数超过任何其他传染病，其中大多数死亡发生在发展中国家，这些国家缺乏获得改进的诊断工具的机会。控制结核病流行的关键是在潜伏性疾病转变为活动性疾病之前及早发现和治疗潜伏性疾病患者。该SBIR项目解决了对用于识别感染潜伏性和活动性结核病（TB）的个体的即时检测的重要需求。基于血清学的测定法很容易适用于护理点资源，然而，对于TB，尚未定义诊断抗原决定簇。在所研究的数十种TB相关抗原中，没有一种是足够免疫显性的，对于基于经典免疫测定的诊断是可靠的。在这个项目中，我们解决这个问题的蛋白质多重微阵列，能够在一个单一的实验中检测，大量的不同的抗体产生的体液反应结核抗原。该测试的诊断能力将随着可以分析的抗原数量的增加而直接增加。观察数百种确定的抗原的能力，以及增加的灵敏度和特异性，应该允许更稳健和准确的分析，可以检测感染的个体并区分感染的潜伏期和活动期。所提出的平台比ELISA形式灵敏几个数量级。这种增加的灵敏度与检测伊加类抗体的容易性相结合（伊加应答通常比免疫受损个体中的IgG应答受影响更小）将允许将该测试用于具有其他共病例如HIV感染的患者。在第一阶段，我们将用有限数量的临床定义样本测试多重微阵列平台的可行性。第二阶段的成功完成将产生一种改进的、快速的结核感染护理点检测和筛查方法。 识别活动性结核病（TB）患者对于预防TB传播的公共卫生保健工作至关重要。然而，准确识别和治疗潜伏性结核病患者对于全面控制这种疾病至关重要。在世界范围内，结核病（TB）造成的死亡人数超过任何其他传染病。改进的结核病诊断服务对免疫受损的个人效果较差，在结核病负担和发病率最高的国家，这种服务极为有限。一种负担得起的、准确的、可获得的免疫测定方法，能够早期识别潜伏性或活动性结核病，对于感染控制计划的成功至关重要。所提出的多重微阵列方法是一种实用、有效的系统来检查特异性、显著的TB抗体。这种用于TB的护理点多重微阵列检测可以在护理点识别潜伏性以及活动性TB感染，因此药物治疗可以更快地开始。

DESCRIPTION (provided by applicant): Worldwide, TB causes more human deaths than any other infectious disease and most of these deaths occur in developing countries where access to improved diagnostic tools is lacking. The key to controlling the TB epidemic is the early identification and treatment of patients with latent disease before conversion to active disease. This SBIR project addresses the important need for a point of care assay for identifying individuals infected with latent and active tuberculosis (TB). Serological based assays are readily adaptable to point-of-care resources, however, for TB, no diagnostic antigen determinants have been defined. Of the dozens of TB- associated antigens investigated, none are sufficiently immunodominant to be reliable for a classical immunoassay based diagnostic. In this project, we address this problem with a protein multiplex microarray that is capable of detecting in a single experiment, a large number of diverse antibodies that are generated in the humoral response to TB antigens. The diagnostic power of the test will increase directly with the number of antigens that can be analyzed. The ability to look at hundreds of defined antigens, with increased sensitivity and specificity should allow a more robust and accurate analysis which can detect infected individuals and differentiate between latent and active stages of infection. The proposed platform is orders of magnitude more sensitive than ELISA formats. This increased sensitivity combined with the ease of detecting IgA class antibodies (IgA response is often less effected than the IgG response in immune-compromised individuals) will permit the use of the test for patients with other co-morbidities e.g. HIV infection. In Phase I, we will test the feasibility of the multiplex microarray platform with a limited number of clinically defined samples. The successful completion of Phase II will produce an improved, rapid, point of care detection and screening assay for TB infection. Identification of individuals with active tuberculosis (TB) is critical to public health care efforts to prevent the spread of TB. However, accurately identifying and treating individuals who have latent TB, is vital to the over-all control of this disease. Worldwide tuberculosis (TB) causes more human deaths than any other infectious disease. Improved TB diagnostic services are less effective in immune compromised individuals and such services are extremely limited in countries with the highest TB burden and morbidity. An affordable, accurate, accessible immunoassay that enables early identification of latent or active TB is crucial for infection control program success. The proposed multiplex microarray methodology is a practical, efficient system to check for specific, significant TB antibodies. This point-of-care multiplex microarray assay for TB can identify at the point-of-care, latent as well as, active TB infection and therefore drug therapy can begin sooner.