The calf model of immunity for development of a vaccine against tuberculosis.
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.
Endsley
Janice J
JJ
University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, United States.
Waters
W Ray
WR
Palmer
Mitchell V
MV
Nonnecke
Brian J
BJ
Thacker
Tyler C
TC
Jacobs
William R
WR
Larsen
Michelle H
MH
Hogg
Alison
A
Shell
Elisabeth
E
McAlauy
Martin
M
Scherer
Charles F Capinosh
CF
Coffey
Tracey
T
Howard
Chris J
CJ
Villareal-Ramos
Bernardo
B
Estes
D Mark
DM
D000818:Animals; D015415:Biomarkers; D002417:Cattle; D004195:Disease Models, Animal; D006801:Humans; D008214:Lymphocytes / Q000502:physiology; D009163:Mycobacterium bovis; D032581:Tuberculosis Vaccines / Q000009:adverse effects / Q000276:immunology*; D014380:Tuberculosis, Bovine / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000517:prevention & control*
D015415:Biomarkers; D032581:Tuberculosis Vaccines