Failure of aMycobacterium tuberculosis[Delta]RD1[Delta]panCDdouble deletion mutant in a neonatal calf aerosolM. bovischallenge model: Comparisons to responses elicited byM. bovisbacille Calmette Guerin

• Published in: Vaccine 2007-11, Vol.25 (45), p.7832
• Main Authors: Waters, W Ray, Palmer, Mitchell V, Nonnecke, Brian J, Thacker, Tyler C, Scherer, Charles F Capinos, Estes, D Mark, Jacobs, William R, Glatman-Freedman, Aharona, Larsen, Michelle H
• Format: Article
• Language: English
• Subjects: Age; Animal diseases; Cattle; Gene expression; Infections; Pathology; Proteins; Studies; Tuberculosis; Vaccines
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2007.08.029

An attenuatedMycobacterium tuberculosis RD1knockout and pantothenate auxotroph (mc26030) vaccine administered at 2 weeks of age failed to protect calves from low dose, aerosolM. bovischallenge at 2.5 months of age. In contrast,M. bovisbacille 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., [arrow down]CD25+ and CD44+ cells and [arrow up]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.