Failure of a Mycobacterium tuberculosis ΔRD1 ΔpanCD double deletion mutant in a neonatal calf aerosol M. bovis challenge model: Comparisons to responses elicited by M. bovis bacille Calmette Guerin

An attenuated Mycobacterium tuberculosis RD1 knockout and pantothenate auxotroph (mc²6030) vaccine administered at 2 weeks of age failed to protect calves from low dose, aerosol M. bovis challenge at 2.5 months of age. In contrast, M. bovis bacille Calmette Guerin (BCG)-vaccinates had reduced tuberculosis-associated pathology as compared to non- and mc²6030-vaccinates. Mycobacterial colonization was not impacted by vaccination. Positive prognostic indicators associated with reduced pathology in the BCG-vaccinated group were decreased antigen induced IFN-γ, iNOS, IL-4, and MIP1-α responses, increased antigen induced FoxP3 expression, and a diminished activation phenotype (i.e., ↓CD25+ and CD44+ cells and ↑CD62L+ cells) in mycobacterial-stimulated mononuclear cell cultures. The calf sensitization and challenge model provides an informative screen for candidate tuberculosis vaccines before their evaluation in costly non-human, primates.