Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Review Article
Publication Acceptance Date: 10/23/2008
Publication Date: 3/15/2009
Citation: Endsley, J., Waters, W.R., Palmer, M.V., Nonnecke, B.J., Thacker, T.C., Jacobs, W.R., Larsen, M., Hogg, A., Shell, L., Mcalauy, M., Capinos-Scherer, C., Coffey, T., Howard, C., Villareal-Ramos, B., Estes, M. 2009. The Calf Model of Immunity for Development of a Vaccine Against Tuberculosis. Veterinary Immunology and Immunopathology. 128(1-3):199-204.
Interpretive Summary: Despite highly successful eradication efforts in several countries, tuberculosis of cattle remains a serious health concern worldwide. In addition, a recent outbreak of tuberculosis in white-tailed deer in Michigan has seriously hindered eradication efforts within the United States. Improved techniques are needed for prevention of tuberculosis in cattle. In this review article, a bovine model for evaluation of improved vaccines and host responses associated with effective responses to tuberculosis are described. Knowledge obtained from studies reviewed in this article will assist in the development of new vaccines for prevention of tuberculosis in cattle.
Technical Abstract: Abstract: Tuberculosis (TB) remains a major public health threat and can be considered a reemerging disease due to many factors and is especially problematic in developing countries where co-infection with HIV significantly increases morbidity and mortality. Vaccination is a low cost and effective strategy for the prevention and therapeutic reduction of infectious diseases. The Bacille Calmette-Guérin (BCG) attenuated live vaccine has been used since 1921 as the sole vaccine to control TB. Protection with BCG however wanes with age, is ineffective for boosting immunity, is highly variable in efficacy, is not recommended for use in immunocompromised patients and has been shown to reactivate in children who later develop HIV. The identification of safe tuberculosis vaccine candidates beyond M. bovis BCG, is an exciting prospect for control of human tuberculosis 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 five 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 tuberculosis 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 will be discussed in addition to end stage effector mechanisms which may limit bacterial growth.