The immunology of bovine tuberculosis and progression toward improved disease control strategies.

Failure to remove cattle diseased with Mycobacterium bovis has immense financial implications for disease control, animal health and agricultural trade as well as the zoonotic risk to human health. Current disease control strategies based on DTH skin testing fail to detect all diseased cattle and additional measures are urgently needed to improve detection of disease and to prevent naïve animals becoming exposed to infection. Experimental models of bovine TB traditionally based on intra-nasal instillation, intra-tracheal inoculation or placed in-contact with infected cattle, have been further developed using aerosolised bacteria delivered to the respiratory tract, allowing field-like bovine TB to be recreated under controlled, experimental conditions. Experimental infection models have already been used to improve diagnostic tests. Specificity of DTH skin testing can be improved under experimental conditions, using recombinant ESAT-6, while laboratory assays such as IFN-gamma release have benefited from the use of defined proteins to improve assay specificity. In combination, antigen cocktails may also improve test sensitivity. There is a concerted international effort to evaluate vaccines for use in cattle populations and to define vaccination strategies which will eliminate disease from infected herds. DNA, protein and genetically modified vaccines inoculated in a single dose, given as prime-boost or injected concurrently, will elicit significant protection against challenge with M. bovis under controlled conditions. However, vaccines and vaccination strategies require evaluation under field conditions. Furthermore, complementary strategies are under development to differentiate immune responses that follow vaccination from those following disease. This paper describes those recent advances which may lead to the introduction of improved disease control strategies.