Proteome screening for tuberculosis outcome markers

描述（由申请方提供）：我们的长期目标是检验以下假设：在结核分枝杆菌感染过程中，抗原特异性免疫应答的特征发生变化，推测与宿主免疫状态应答中发生的细菌抗原组成变化有关。血清抗体谱的变化与M.将在非人灵长类动物模型中用最先进的高通量筛选~500蛋白M来测量结核病。结核病微阵列芯片，使用已经从表现出活动性疾病或潜伏感染的食蟹猴连续收集的血清，有/没有随后的再活化。在抗体筛选中鉴定的靶抗原将被进一步纯化，并用于在正在进行的实验感染过程中监测抗原特异性T细胞应答。在灵长类动物中鉴定结果特异性免疫谱有望帮助鉴定从潜伏感染进展到活动性结核的人类免疫标记物，这些标记物在活动性疾病的临床或细菌学指标之前可检测到。在猕猴中鉴定感染结果的标志物也将提高非人灵长类动物结核病模型用于疫苗和药物评价的价值。

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.