Proteome screening for tuberculosis outcome markers

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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.