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Tuberculosis Diagnostics
The Challenge
Existing TB diagnostics pose significant hurdles for routine use: they can be too time-consuming, complicated, labor-intensive, inaccurate, or expensive . They also frequently fail to detect disease in extra-pulmonary TB patients, children, and in patients co-infected with HIV. Together, these drawbacks amount to missed or significantly delayed diagnoses, which contribute to Mycobacterium tuberculosis transmission and increased TB-related mortality. A simple, accurate and cost-effective point-of-care test for TB has long been sought. Immunodiagnostic assays remain attractive, especially for use in resource-limited settings, because they are generally easy-to-perform, rapid, and relatively inexpensive.
Our Solutions
Our scientists harnessed the latest genomic and proteomic tools to characterize the molecular targets of the host immune response to MTB. This has allowed us to better understand the specific immune responses associated with tuberculosis disease progression, disease resolution, and the development of latency.
From this work, we have produced the world's largest collection of TB antigens and screened them for the ability to detect antibody from TB patients with active disease. We have identified a panel of novel and previously characterized antigens with promising immunodiagnostic potential. Due to the heterogeneity of the antibody response observed in TB patients and a lack of dominant antigen responses, multiple antigens are needed to achieve target sensitivities and specificities. We are currently optimizing antigen combinations to increase performance in simple lateral flow assay formats for the development of effective, low-cost diagnostic tests for TB that may be used in low-resource settings.
Publications
Houghton, R. L., Lodes, M. J., Dillon, D. C., Reynolds, L. D., Day, C. H., McNeill, P. D., Hendrickson, R. C., Skeiky, Y. A., Sampaio, D. P., Badaro, R., Lyashchenko, K. P., and Reed, S. G. (2002) Use of multiepitope polyproteins in serodiagnosis of active tuberculosis, Clinical and diagnostic laboratory immunology 9, 883-891.
Ireton, G. C.*, Bertholet, S.*, Kahn, M., Guderian, J., Mohamath, R., Stride, N., Laughlin, E. M., Baldwin, S. L., Vedvick, T. S., Coler, R. N., and Reed, S. G. (2008) Identification of human T cell antigens for the development of vaccines against Mycobacterium tuberculosis, J Immunol 181, 7948-7957.
Ireton, G. C., Greenwald, R., Liang, H., Esfandiari, J., Lyashchenko, K. P., and Reed, S. G. (2010) Identification of Mycobacterium tuberculosis antigens of high serodiagnostic value, Clin Vaccine Immunol 17, 1539-1547.
Key Scientists
Greg Ireton
Rhea Coler
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