Tuberculosis vaccination: microbiological and immunological summary of a series of experimental challenge studies

The complexity of bovine tuberculosis (TB) epidemiology, especially in extensive livestock systems with wildlife reservoirs, calls for novel control strategies such as vaccination. This study evaluated the comparative efficacy of homologous and heterologous inactivated vaccines against that of the live Bacille Calmette–Guérin (BCG) vaccine on M. bovis isolation, gross TB lesions, and immune responses. Data from four controlled vaccination and challenge trials involving 41 calves were analysed. Animals were vaccinated with live BCG or heat-inactivated M. bovis via oral or parenteral routes, and immunologic and post-mortem analyses were conducted to evaluate vaccine performance. Compared with nonvaccinated controls, all vaccination strategies significantly reduced M. bovis bacterial loads in the lungs (up to 99%). However, bacterial loads in lymphoid tissues increased, confirming that tuberculosis is primarily a lymphatic disease. Diagnostic interference varied by vaccine type and administration route, with oral administration resulting in lower interference. Gross lesion scores were inconsistent across groups, suggesting limited utility as a measure of vaccine efficacy. Immune responses revealed increased detection of infection, particularly with inactivated vaccines. The lung bacterial load appeared to be decoupled from cellular immune responses, lymph node lesions and bacterial load, which were negatively correlated. Inactivated vaccines can offer a safe and effective means of reducing the bovine TB reproductive rate (R₀) even without total bacterial clearance. These findings highlight the need for revised evaluation criteria and support the integration of inactivated vaccines into TB control strategies.