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The development of improved tests for the diagnosis of Mycobacterium bovis infection in cattle - SE3028

Description
Current diagnostic tests for the detection of M. bovis infection in cattle (e.g. skin test or IFN- test) rely on the use of tuberculin PPDs as antigens. However, the cross reactivity with M. bovis of cell-mediated responses induced by other species of mycobacteria reduces the specificity of tuberculin based tests. Moreover, use of a cattle vaccine is effectively prohibited by the current EU legislation because it would compromise the current tuberculin test. Antigens whose genes are expressed in M. bovis yet absent from environmental mycobacteria (like M. avium) or vaccines (such as BCG) constitute candidates for inclusion in diagnostic reagents, which are both defined and more specific than PPD. In general, gains in specificity using defined antigens have been offset by losses in sensitivity. However, we have recently developed a cocktail of antigens that is more specific than tuberculin when used in a whole blood gamma interferon assay and results in test sensitivities approaching tuberculin (80% vs. 88%). In addition, this cocktail can be used to discriminate between BCG vaccinated and M. bovis infected cattle. The main purpose of this proposal is to identify further specific antigens with which to increase the sensitivity of the IFN- test to levels achieved with tuberculin. Our approach utilises the availability of the genome sequences of several mycobacterial genomes (M. tuberculosis, M. bovis, BCG, M.avium, M. paratuberculosis) by applying principles of comparative genomics to the identification of species-specific antigens. These antigens will then be screened in the form of synthetic peptides for their antigenicity in uninfected cattle or cattle infected with M. bovis or M. paratuberculosis. A further objective of this proposal is to develop platform technology that allows the simultaneous measurement of multiple immunological parameters within the same sample. The approaches outlined in this proposal will lead to refinements of current diagnostic strategies for bovine tuberculosis and therefore address the research needs identified in the DEFRA Research Requirement Document (R.24).
Objective
Objective 1: The use of comparative genomics to identify more specific reagents to detect bovine TB in cattle (VLA) 04/04

Objective 2: Validation of diagnostic potential of antigens identified in obj. 1 in non-infected, M. bovis, and M. paratuberculosis infected cattle (VLA, VSD, VAR) 03/05

Objective 3: Exchange information to coordinate research efforts at VLA Weybridge and VSD, DANI, Belfast 03/05

Objective 4: Development and validation of a novel platform technology allowing high throughput, simultaneous and cost-effective multiparameter diagnosis based on biosensor technology (VLA, VAR, Lionex) 03/05 03/05
Project Documents
• Final Report : The development of improved tests for the diagnosis of Mycobacterium bovis infection in cattle   (668k)
Time-Scale and Cost
From: 2002

To: 2005

Cost: £428,428
Contractor / Funded Organisations
Veterinary Laboratories Agency
Keywords
Animal Health              
Biotechnology              
Bovine Tuberculosis              
Control              
Diagnosis              
Plants and Animals              
Zoonoses              
Fields of Study
Animal Health