SBIR-STTR Award

With eight million cases arising each year worldwide, tuberculosis (TB) is the leading cause of death from a single infectious agent. Identification of diseased individuals is crucial for TB control, because rapid diagnosis usually leads to timely initiation of therapy. The only current method for rapid TB diagnosis is microscopic examination of sputum smears. In low-income countries with high- prevalence of TB, sputum smear microscopy often has unacceptably low sensitivity. Other methods being developed are likely to be unaffordable. The overall goal of the proposed work is to develop a rapid, simple, accurate, and inexpensive serodiagnostic assay for TB. The test will require one drop of whole blood, no equipment and no skilled personnel, and will take only a few minutes to execute and to read. An accurate serodiagnostic assay must be based on multiple antigens of Mycobacterium tuberculosis, because antibodies produced by TB patients react with a board number of antigens. Work proposed for Phase I project will identify the most suitable for a rapid immunoassay format among many (at least twelve) serologically reactive, purified recombinant antigens. Selected antigens will be used to formulate multi-antigen cocktails. A multi-antigen cocktail yielding a highly accurate serodiagnostic assay will be developed into a commercial diagnostic kit for TB during Phase II. PROPOSED COMMERCIAL APPLICATION: Development of rapid point of care serodiagnostics that can be utilized in both laboratory and non-laboratory settings by non-skilled persons. Such a test would provide on the spot determination of TB infection status allowing for immediate therapeutic treatment to being. Such as test would be a low cost alternative to time consuming culture/smear and/or x-ray and be an economic alternative especially in developing countries.

Thesaurus Terms:
diagnosis design /evaluation, diagnosis quality /standard, method development, rapid diagnosis, serology /serodiagnosis, tuberculin test, tuberculosis Mycobacterium tuberculosis, bacterial antigen, recombinant protein, respiratory disorder diagnosis clinical research, enzyme linked immunosorbent assay, human tissue

Control of tuberculosis (TB), a disease that causes 3 million deaths a year worldwide, requires rapid methods for timely diagnosis. The goal of the proposed work is to develop a simple, rapid, accurate and inexpensive serodiagnostic assay for active TB using a thin-layer immunochromatography (TLIC) format and multiple recombinant antigens of Mycobacterium tuberculosis. Serodiagnostic tests for TB require multiantigen cocktails because of patient-to-patient variation in recognition of antigens by serum antibodies. Phase I studies have already identified eight antigens suitable for cocktail development and demonstrated that TLIC methodology is applicable to multiantigen-based TB serodiagnostics. Work proposed for Phase II is expected 1) to advance test development in terms of antigen composition and assay conditions, 2) to validate the diagnostic performance of selected cocktails in different TB cohorts and control groups, and 3) to establish methodologies for batch production of antigens. The goal of Phase II studies is to develop a test having a specificity close to 100% and a sensitivity of 90% in smear-positive pulmonary TB. The commercial opportunities for a rapid serodiagnostic TB test having the proposed specifications are immense.

Thesaurus Terms:
diagnosis design /evaluation, diagnosis quality /standard, rapid diagnosis, serology /serodiagnosis, thin layer chromatography, tuberculin test, tuberculosis Mycobacterium tuberculosis, bacterial antigen, method development, recombinant protein, respiratory disorder diagnosis enzyme linked immunosorbent assay, human tissue