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

W. Ray Waters, Mitchell V. Palmer, Brian J. Nonnecke, Tyler C. Thacker, Charles F.Capinos Scherer, D. Mark Estes, William R. Jacobs, Aharona Glatman-Freedman, Michelle H. Larsen

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7832-7840
Number of pages9
JournalVaccine
Volume25
Issue number45
DOIs
StatePublished - Nov 7 2007

Keywords

  • Aerosol Inoculation
  • Auxotroph
  • BCG
  • FoxP3
  • Live bacterial vaccine
  • Neonatal calf
  • Tuberculosis

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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