An independent review for the British government has concluded that the development of a cattle
vaccine against Mycobacterium bovis holds the best long-term prospects for
tuberculosis control in British herds. The development of complementary diagnostic tests to differentiate between vaccinated and infected animals is necessary to allow the continuation of test-and-slaughter-based control policies alongside vaccination. Vaccination with M. bovis bacillus Calmette-Guérin (BCG), the only available
vaccine, results in
tuberculin purified
protein derivative sensitivity and has shown varying
vaccine efficacies in cattle. Thus, identification of more-specific
reagents to distinguish between vaccination and
infection, as well as the identification of
subunit vaccine candidates for improved
tuberculosis vaccines, is a research priority. In the present study, we applied comparative genomics to identify M. bovis-
Mycobacterium tuberculosis antigens whose genes had been deleted in BCG Pasteur. In total, 13 open reading frames (ORFs) from the RD1, RD2, and RD14 regions of the M.
tuberculosis genome were selected. Pools of overlapping
peptides spanning these ORFs were tested in M. bovis-infected (n = 22), BCG-vaccinated (n = 6), and unvaccinated (n = 10) control cattle. All were recognized in infected cattle, with responder frequencies varying between 16 and 86%. In particular, eight highly immunogenic
antigens were identified whose potentials as diagnostic
reagents or as
subunit vaccines warrant further study (Rv1983, Rv1986, Rv3872, Rv3873, Rv3878, Rv3879c, Rv1979c, and Rv1769).