Bovine Tuberculosis Vaccine Programme
Programme Leaders: Prof Glyn Hewinson and Dr Martin Vordermeier
Bovine tuberculosis (TB), caused by the bacterium Mycobacterium bovis, is acknowledged as one of the most difficult animal health problems currently facing the farming industry in Great Britain. Despite the test-and-slaughter policy for cattle, the incidence of TB remains high with implications for animal health and welfare, in addition to causing major economic losses. The overall cost of bovine TB control has also increased several fold since 1999 to around £100 million in 2011. This, combined with the potential for bovine TB to cause disease in people, has maintained the impetus for understanding and controlling this disease.
It is recognized that elimination of the disease in cattle will depend on effective vaccines and sensitive, specific diagnostic tests. Vaccination has been proposed as a possible control measure. The attenuated strain of M. bovis bacillus Calmette-Guerin (BCG) is to date the most successful vaccine against TB in humans and has also been used to vaccinate cattle. However, the efficacy of BCG has in cattle has been variable, although a significant degree of protection has been established in most studies undertaken in cattle and cattle. Efforts are underway to license BCG for cattle. It is however, also acknowledged that its efficacy has to be improved. A number of strategies including heterologous prime boost approaches using BCG to prime responses and subunit vaccines such as virally vectored constructs to boost the immune system. To continue with the existing test and cull control policy it is also necessary to develop ante-mortem diagnostic strategies that do not interfere with vaccination, so-called DIVA reagents (Differentiation of Infected from Vaccinated Animals).
The immune response to mycobacteria is complex and although necessary for protection also contribute to disease development (pathogenesis). To determine the distinction between protective and pathogenic immune responses during bovine TB is an absolute requirement for the development of more efficacious and safer vaccines.
Parallel human-veterinary vaccine development
Jenner Investigators, Dr. Martin Vordermeier and Prof. Glyn Hewinson of the Animal Health and Veterinary Laboratories Agency are testing the protective efficacy of prime-boost vaccination regimens as currently being tested in the Human TB Vaccine Programme. The protective efficacy of these regimens will be related to the immune responses induced.
These experiments will help develop correlates of immunity to TB and may contribute not only to the development of safer vaccines but also to the development of improved diagnostics responses. Further, they are involved in experiments defining biomarkers that predict or correlate with vaccine success, or alternatively correlate with disease progression and could therefore be used as novel diagnostic assets.
The programme is also working on the development of DIVA assays applying comparative genome and transcriptome approaches to define specific DIVA antigens.