Bovine TB: Research project summary
Project SE3208: Generation of vaccine candidates against Mycobacterium bovis.
Project duration: 6 years
The aim of this project was to use recent scientific advances in the bovine TB field to generate and test vaccine candidates against Mycobacterium bovis (M. bovis) infection. Several approaches were taken, the first one was the rational attenuation of M. bovis. Various strategies for generating live attenuated vaccines were tried where key genes essential for growth and survival of M. bovis within the host were inactivated. The desired result is a vaccine that is disabled but sufficiently robust to induce a protective immune response. The project generated a number of vaccine candidates that were as good as BCG in protecting guinea pigs from virulent infection. Future work will be required on these potential vaccines to confirm the results, to characterise them further, to investigate them as potential vaccines in other hosts, to assess the host immune responses, to remove antibiotic resistance genes and, to incorporate another attenuating mutation so that there is no chance the vaccine can revert back to virulence.
The second approach was to produce a subunit vaccine composed of either DNA or protein components. The candidates used were identified as being dominant for the immune response in other contracts (SE3212, SE3210). A number of promising candidates were found in guinea pigs but protection was not found in cattle. One vaccine made lung pathology worse.
The last approach combined the previous two and was based on a heterologous prime boost strategy. This is the same strategy that is being pursued for human TB vaccination. Here the efficacy of BCG is improved upon by boosting with a subunit vaccine. Various subunits were tried and some were found to improve on the protection of BCG alone. Importantly the choice of adjuvant that helps present the subunit vaccine to the immune response turns out to be just as important as the subunit vaccine component itself. These vaccine candidates are being taken forward under Defra contract SE3224.
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Page last modified:
July 7, 2008