title: 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.
abstract: 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.
authors.affiliation: National Animal Disease Center, Agricultural Research Service, US Department of Agriculture, 2300 Dayton Avenue, Ames, IA 50010, USA. ray.waters@ars.usda.gov
authors.forename: W Ray
authors.initials: WR
authors.lastname: Waters
authors.forename: Mitchell V
authors.initials: MV
authors.lastname: Palmer
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Nonnecke
authors.forename: Tyler C
authors.initials: TC
authors.lastname: Thacker
authors.forename: Charles F Capinos
authors.initials: CF
authors.lastname: Scherer
authors.forename: D Mark
authors.initials: DM
authors.lastname: Estes
authors.forename: William R
authors.initials: WR
authors.lastname: Jacobs
authors.forename: Aharona
authors.initials: A
authors.lastname: Glatman-Freedman
authors.forename: Michelle H
authors.initials: MH
authors.lastname: Larsen
mesh_terms: D000336:Aerosols; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000276:immunology; D002417:Cattle; D002478:Cells, Cultured; D017353:Gene Deletion; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014611:Vaccination / Q000379:methods
chemical_list: D000336:Aerosols; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; D032581:Tuberculosis Vaccines