Recombinant and synthetic peptides to identify Mycobacterium tuberculosis antigens and epitopes of diagnostic and vaccine relevance

The failures of Bacillus Calmette Guerin (BCG) as a vaccine and purified protein derivative as a diagnostic reagent in controlling the worldwide prevalence of tuberculosis (TB) have accelerated the research to identify Mycobacterium tuberculosis-specific antigens that could be useful as new vaccines and diagnostic reagents against TB. In the recent years, the comparative analyses of M. tuberculosis genome with the genomes of other mycobacteria have led to the identification of several genomic regions of M. tuberculosis that are deleted in BCG and other mycobacteria. These deleted regions (RDs) are predicted to encode over 100 proteins. If found immunologically reactive, the proteins encoded by M. tuberculosis-specific RDs could be useful in the specific diagnosis of TB and developing new vaccines. Among the approaches available for immunological characterization of the predicted M. tuberculosis-specific proteins are the evaluations of recombinant proteins and/or overlapping synthetic peptides, covering the sequence of each protein, for antibody and/or Th1 cell reactivity. These approaches have resulted into the identification of several antigenic proteins of M. tuberculosis encoded by genes located in RD1 with potentials in specific diagnosis of TB in tow endemic areas and/or development of new vaccines, e.g. ORF14, ESAT6, CFP10, PE, PPE proteins, etc. In addition, prediction programs to identify peptides that could bind several HLA molecules, and presented to T-cells in a promiscuous manner, have been developed. These programs have been used, on a limited scale, to identify the promiscuous peptides encoded by the genes spanning the M. tuberculosis-specific sequence. The promiscuous antigens/peptides recognized by T-cells in cell mediated immunity assays may have potentials in developing peptide-based vaccines and diagnostic reagents against TB. (c) 2005 Elsevier Ltd. All rights reserved.