Proteome screening for tuberculosis outcome markers

描述（由申请人提供）：我们的长期目标是验证抗原特异性免疫反应在结核分枝杆菌感染过程中发生变化的假设，可能与宿主免疫状态下细菌抗原组成的变化有关。血清抗体谱与结核分枝杆菌结果相关的变化将在非人灵长类动物模型中进行测量，该模型采用最先进的、高通量筛选约500蛋白结核分枝杆菌微阵列芯片，该芯片使用已经从患有活动性疾病或潜伏性感染的食蟹猴连续收集的血清进行检测。在抗体筛选中确定的靶抗原将被进一步纯化，并用于监测正在进行的实验感染过程中的抗原特异性T细胞反应。鉴定灵长类动物的结果特异性免疫谱有望帮助鉴定人类从潜伏感染到活动性结核病进展的免疫标记物，这些标记物在活动性疾病的临床或细菌学指标之前可被检测到。鉴定猕猴感染结果的标记也将提高非人类灵长类结核病模型在疫苗和药物评价中的价值。

DESCRIPTION (provided by applicant): Our long-term goal is to test the hypothesis that profiles of antigen-specific immune responses vary over the course of infection with Mycobacterium tuberculosis, presumably in relation to changes of bacterial antigen composition occurring in response to host immune status. Changes in serum antibody profiles relative to outcome of M. tuberculosis will be measured in a non-human primate model with state-of-the-art, high-throughput screening of a ~500-protein M. tuberculosis microarray chip using sera already collected serially from cynomolgus macaques exhibiting either active disease or latent infection with/without subsequent reactivation. Target antigens identified in the antibody screen will be further purified and used for monitoring antigen-specific T cell responses over the course of ongoing experimental infection. Identification of outcome-specific immune profiles in primates is expected to help identify human immune markers of progression from latent infection to active tuberculosis that are detectable before clinical or bacteriological indicators of active disease. Identification of markers of infection outcome in macaques would also enhance the value of non-human primate models of tuberculosis for vaccine and drug evaluation.