Influence of sensitisation to environmental mycobacteria on subsequent vaccination against bovine tuberculosis.

Bacille Calmette-Guerin (BCG) is the world's most widely used vaccine, but there are concerns that it provides little protection against pulmonary tuberculosis of humans in countries that have a high prevalence of environmental mycobacteria. Experiments in cattle provide a model to investigate this situation and to develop an improved tuberculosis vaccine. In the third of a series of BCG vaccination trials, calves had high interferon-gamma (IFN-gamma) responses to purified protein derivative (PPD) from Mycobacterium avium prior to vaccination, indicating that infection with environmental mycobacteria had occurred. The calves vaccinated with BCG had minimal protection against an experimental intratracheal challenge with virulent Mycobacterium bovis. In comparison, calves vaccinated with either of two newly-derived attenuated M. bovis strains had significantly better but not complete protection against the development of tuberculous lesions compared to both BCG-vaccinated and non-vaccinated animals. Vaccination with the newly-derived attenuated M. bovis strains induced strong IFN-gamma and interleukin-2 (IL-2) responses to PPD from M. bovis at 2 weeks after vaccination, while BCG vaccination induced only a weak response at this time. In association with the previous two trials, the results suggest that sensitisation of the calves to environmental mycobacteria adversely affected subsequent protective efficacy of BCG. However, the results of vaccination with the other two attenuated M. bovis strains indicated that improved tuberculosis vaccines could be developed for such sensitised animals.