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 Citations (Scopus)

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

Fingerprint

Mycobacterium bovis
Mycobacterium tuberculosis
aerosols
Aerosols
tuberculosis
Tuberculosis Vaccines
calves
Pathology
vaccines
antigens
auxotrophs
Antigens
mutants
interleukin-4
Interleukin-4
Primates
Vaccination
Tuberculosis
cell culture
Vaccines

Keywords

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

ASJC Scopus subject areas

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

Cite this

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. / 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.

In: Vaccine, Vol. 25, No. 45, 07.11.2007, p. 7832-7840.

Research output: Contribution to journalArticle

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. / 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. In: Vaccine. 2007 ; Vol. 25, No. 45. pp. 7832-7840.
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