Frequency of IFN-γ producing cells correlates with adjuvant enhancement of bacille Calmette-Guèrin induced protection against Mycobacterium bovis

Tuberculosis caused by infection with Mycobacterium tuberculosis or Mycobacterium bovis remains one of the most important infectious diseases of man and animals. The current vaccine M. bovis Calmette-Guérin (BCG) demonstrates variable efficacy and so a more robust strategy to either replace, or more likely supplement it, is required. Prime-boost strategies where immunity induced by BCG is boosted by a second heterologous vaccine represent a promising avenue of research. We have evaluated the ability of a protein subunit vaccine using the antigen Rv3019c to either prime or boost immunity induced by BCG in a murine M. bovis challenge model. Despite the induction of anamnestic T cell responses, we report that antigen-independent immune stimulation with adjuvant in conjunction with BCG could enhance the level of protection induced by BCG alone. Importantly this improved protection correlated with pre-infection frequencies of ex vivo IFN-γ producing cells in the spleen, providing a possible surrogate correlate of protection for future vaccination studies.