The calf model of immunity for development of a vaccine against tuberculosis

Authors Organisations
  • Janice J. Endsley(Author)
    University of Texas Medical Branch
  • W. Ray Waters(Author)
    Bacterial Diseases of Livestock Research Unit
  • Mitchell V. Palmer(Author)
    Bacterial Diseases of Livestock Research Unit
  • Brian J. Nonnecke(Author)
    Bacterial Diseases of Livestock Research Unit
  • Tyler C. Thacker(Author)
    Bacterial Diseases of Livestock Research Unit
  • William R. Jacobs(Author)
    Howard Hughes Medical Institute
  • Michelle H. Larsen(Author)
    Howard Hughes Medical Institute
  • Alison Hogg(Author)
    University of Texas Medical Branch
  • Elisabeth Shell(Author)
    University of Texas Medical Branch
  • Martin McAlauy(Author)
    Institute of Animal Health
  • Charles F.Capinosh Scherer(Author)
    University of Texas Medical Branch
  • Tracey Coffey(Author)
    Institute of Animal Health
  • Chris J. Howard(Author)
    Institute of Animal Health
  • Bernardo Villarreal-Ramos(Author)
    Institute of Animal Health
  • D. Mark Estes(Author)
    University of Texas Medical Branch
Type Article
Original languageEnglish
Pages (from-to)199-204
Number of pages6
JournalVeterinary Immunology and Immunopathology
Volume128
Issue number1-3
Early online date18 Oct 2008
DOI
Publication statusPublished - 15 Mar 2009
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Abstract

Tuberculosis (TB) remains a major threat to public health. The identification of safe TB vaccine candidates beyond Mycobacterium bovis BCG, is an exciting prospect for control of human TB and necessary in the context of the human immunodeficiency virus (HIV) pandemic. Selection of vaccine candidates for human trials which are ultimately targeted for use in children less than 5 years of age or in newborns will require an animal model that closely approximates immune function and disease. We propose that the bovine neonate and adolescent is a robust animal model for preclinical safety and efficacy evaluation of TB candidate vaccines targeting this special human population. Parallel studies conducted in bovine neonates and non-human primates with a leading auxotrophic mutant with demonstrated efficacy/safety in a rodent TB model of TB demonstrated similar findings with respect to gross pathology scoring relative to BCG. The findings indicated more numerous and severe lesions in the lung in addition to higher levels of IFN-gamma producing cells. BCG vaccinates demonstrated higher levels of FoxP3 transcripts and lower levels of IL-4 mRNA.

Keywords

  • markers, neonatal calf, prognostic, Tuberculosis