Cell mediated immunity assays identify proteins of diagnostic and vaccine potential from genomic regions of difference of mycobacterium tuberculosis

ABSTRACT

Tuberculosis [TB] is a health problem of global concern. To control TB, tuberculin and BCG have been used as diagnostic reagent and vaccine, respectively. However, BCG has failed to provide consistent protection in different parts of the world, and tuberculin has poor specificity due to the presence of crossreactive antigens. Therefore, there is an urgent need to identify M. tuberculosis-specific antigens as new vaccines and diagnostic reagents to control the global epidemic of TB. The advances in comparative genomics have identified 11 genomic regions of My cobacterium tuberculosis, which are deleted/absent in all vaccine strains of BCG currently used to immunize against TB. By using overlapping synthetic peptides corresponding to 89 predicted proteins of these regions of difference [RDs] in cell mediated immunity [CMI] assays, attempts have been made to identify the RDs and antigens with potential in specific diagnosis and development of new vaccines against TB. The most promising regions [antigens] identified for diagnostic applications are RD1 [ESAT-6 and CFP10], and for vaccine applications are RD1 [PPE68], RD7 [Rv2346c and Rv2347c] and RD9 [Rv3619 and Rv3620]. The promise of ESAT-6 and CFP10 in the diagnosis of latent and active TB has been demonstrated in industrialized and low-burden countries, but more work is needed in poor and high-burden countries to establish the utility of these high cost tests in specific diagnosis and epidemiology of TB. Furthermore, the vaccine application of RD antigen requires additional experiments to confirm their protective efficacy in animal models of TB, before they are evaluated in humans