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Vaccine. 2007 Nov 7;25(45):7832-40. Epub 2007 Sep 4.

Failure of a Mycobacterium tuberculosis DeltaRD1 DeltapanCD double deletion mutant in a neonatal calf aerosol M. bovis challenge model: comparisons to responses elicited by M. bovis bacille Calmette Guerin.

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National Animal Disease Center, Agricultural Research Service, US Department of Agriculture, 2300 Dayton Avenue, Ames, IA 50010, USA.


An attenuated Mycobacterium tuberculosis RD1 knockout and pantothenate auxotroph (mc(2)6030) 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 mc(2)6030-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-gamma, iNOS, IL-4, and MIP1-alpha responses, increased antigen induced FoxP3 expression, and a diminished activation phenotype (i.e., downward arrow CD25+ and CD44+ cells and upward arrow 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.

[Indexed for MEDLINE]

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