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Antigen Mining, DIVA Assays and Other Diagnostic Approaches


<p>The prototype DIVA test based on Interferon-gamma testing and using 3 different antigens (ESAT-6, CFP-10, Rv3615c) needs further improvement to achieve test sensitivity levels comparable with those achieved with tuberculin. Further, an alternative DIVA test format based on skin testing would have a number of advantages compared to blood tests including potentially lower costs and easier acceptance by stakeholders and legislators including the EU. In project SE3233 we have provided proof of principle that the same antigens used in the Interferon-gamma DIVA test can also function as skin test antigens, although more antigens will be needed to improve signal strength and sensitivity.</p>

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<p>The incidence of bovine tuberculosis in GB had been increasing since 1988 despite the use of a control strategy based on tuberculin skin testing and slaughter of animals that react positively to the test and remains high. The development of vaccination strategies for cattle is an important part of Defra's research into future control strategies. In order to allow cattle vaccination to become a viable control policy option, diagnostic tests are required that can differentiate between infected and vaccinated cattle, so-called DIVA tests (Differention of Infected and Vaccinated Animals). This is also an important consideration to obtain legal approval from the EU to allow cattle vaccination This project is therefore aimed at the continued development and optimisation of such reagents and approaches.</p>

<p>Building on these previous projects, we therefore propose to continue the multi-track approach taken in SE3233 in this proposal. The applied research part of the project is focused at validation of antigens for tests like the DIVA Interferon-gamma, the DIVA skin test as well as tests using novel biomarkers identified in project SE3233. The basic research approach will focus on the discovery of novel biomarker signatures that could support diagnosis and a risk-based approach to TB control, alone or in combination with vaccination by comparing test-positive visibly lesioned animals with those presenting without lestions (VL versus NVL). Although this project is aimed at DIVA tests, its focus is wider by addressing novel diagnostic approaches and antigen mining for subunit vaccination which directly feeds into the associated proposal of developing vaccines that do not sensitise tuberculin skin test activity.</p>

<p>Outcomes of this project will be further insights into diagnostic strategies that underpin policy development for the use of cattle vaccination including the development of non-sensitising vaccines. Specifically, this will include development of further improved diagnostic reagents that allow the differentiation of vaccinated and infected cattle so that test sensitivities approaching that of tuberculin can be reached. These strategies could be based on an improved version of the interferon-gamma assay, a multiplex blood test or, indeed, a DIVA skin test. In addition, antigens identified during this antigen mining operation will also be assessed for their suitability as potential subunit vaccine candidates. This project will furthermore provide a better understanding on disease progression and latency and a test that can discriminate between active and latent TB would support and underpin a risk-based approach to the control of this disease. </p>

Veterinary Laboratories Agency, UK
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