Genetic screening for the protective antigenic targets of BCG vaccination

Bovine tuberculosis (bTB) is an important animal health problem and the predominant cause of zoonotic tuberculosis worldwide. It results in serious economic burden due to losses in productivity and the cost associated with control programmes. This burden is disproportionally placed on low and middle income countries. Control strategies could be greatly improved by the introduction of an efficacious cattle vaccine. Bacille Calmette Guérin (BCG) displays variable efficacy at population and individual animal levels. Augmentation of BCG with a subunit vaccine booster has been show to increase BCG protection. However, a rational, rather than a serendipitous, approach to the identification of protective antigens for use in a subunit vaccine will be key to its ultimate success. In the present study we selected aBCG transposon mutant library in naïve and BCG-vaccinated cattle to identify the putative protective antigens of BCG. Ten mutants had increased relative survival in vaccinated compared to naïve cattle, consistent with loss of protective antigen targets making the mutants less visible to the BCG immune response. The immunogenicity of three of these putative protective antigens were investigated using peptide pools and PBMCs harvested from BCG vaccinated cattle. BCG vaccination induced PBMC to release elevated levels of IP10, IL-17a and IL-10 in response to all three antigens. Taken together, the data supports the further study of these antigens for use in subunit vaccines.