Identification of an immune response correlate for protection against
bovine tuberculosis would greatly facilitate the rational development of an effective
vaccine. However, finding such a correlate has been a daunting task. Vaccination/challenge studies in cattle provide an ideal platform to compare induction of immune response parameters following vaccination and challenge, and assess the correlation of these parameters with protection. Protection against
tuberculosis requires a Th 1-type cell-mediated immune response and induction of an
antigen-specific
interferon-gamma (IFN-gamma) response was the logical first choice in an investigation to identify an immune response correlate for protection. Calf vaccination studies showed that the
subcutaneous injection of
BCG vaccine induced significant protection against experimental challenge with Mycobacterium bovis. This protection was associated with strong whole blood IFN-gamma responses to bovine
PPD 2-4 weeks after vaccination, but within the BCG-vaccinated groups, these responses were not correlated with protection. Use of a variety of vaccination strategies has shown that IFN-gamma responses in isolation were not necessarily associated with protection and concurrent
IL-4 mRNA expression or antibody responses could also be induced. Collation of an immunological profile may be more informative than a study of individual
cytokines. An indication of
vaccine efficacy can be provided by the study of immune responses following challenge of the calves with M. bovis. IFN-gamma responses to ESAT-6, antibody responses following
tuberculin skin testing and
antigen-specific
IL-4 mRNA expression all correlated with the severity of disease and indirectly provided an indication of protection. Future studies should be directed towards obtaining immunological profiles of calves following vaccination using techniques such as
DNA microarray analysis, measurement of
cytokine mRNA expression by real-time PCR,
protein profiling by SELDI-TOF mass spectrometry as well as determining
cytokine production by specific T cell sub-sets in individual protected animals.