Pathological, microbiological and immunological performance of three tuberculosis vaccine candidates in goats

Test and cull-based animal tuberculosis eradication programs have not succeeded in eliminating TB in various regions and implementing those programs is not feasible in others. Vaccination represents an additional control tool under study. Here we evaluated the immunologic, pathologic, and microbiological effects of heat-inactivated Mycobacterium bovis (HIMB), phage-inactivated Mycobacterium caprae (PIMC) and live Mycobacterium microti (LMM) subcutaneous vaccination in goats challenged endotracheally with M. caprae. All three vaccines were compatible with interferon-γ release assay diagnosis using defined antigens but interfered slightly when this test was performed using standard tuberculins. HIMB and PIMC candidates induced a strong anti-MPB70/MPB83 humoral response, and a modest but significant increase in phagocytic activity and/or reactive oxygen species production by peripheral neutrophils and monocytes, features not observed with LMM vaccination. Vaccination significantly reduced the lung and total lesion severity score (by HIMB, PIMC and LMM; 54, 44 and 52%, respectively), the total lesioned lymph node volume (by LMM), the total mineralized lung volume (by HIMB and LMM) and the mineralized proportion of lung lesions (by HIMB). The bacterial burden of respiratory lymph nodes was reduced in vaccinates by 2.3 (HIMB), 1.9 (PIMC) and 2.1 (LMM) Log₁₀ in comparison to the non-vaccinated infected control. Extra-respiratory pathological and microbiological evidence of infection was mainly restricted to goats from the non-vaccinated infected group. Vaccination with all three prototypes modulated the response of goats against M. caprae experimental challenge leading to varying levels of protective efficacy, highlighting the need for further optimization and research.