Immunological Characterization of Proteins Expressed by Genes Located in Mycobacterium tuberculosis-Specific Genomic Regions Encoding the ESAT6-like Proteins

Abstract

The 6 kDa early secreted antigen target (ESAT6) is a low molecular weight and highly immunogenic protein of Mycobacterium tuberculosis with relevance in the diagnosis of tuberculosis and subunit vaccine development. The gene encoding the ESAT6 protein is located in the M. tuberculosis-specific genomic region known as the region of difference (RD)1. There are 11 M. tuberculosis-specific RDs absent in all of the vaccine strains of BCG, and three of them (RD1, RD7, and RD9) encode immunodominant proteins. Each of these RDs has genes for a pair of ESAT6-like proteins. The immunological characterizations of all the possible proteins encoded by genes in RD1, RD7 and RD9 have shown that, besides ESAT-6 like proteins, several other proteins are major antigens useful for the development of subunit vaccines to substitute or supplement BCG. Furthermore, some of these proteins may replace the purified protein derivative of M. tuberculosis in the specific diagnosis of tuberculosis by using interferon-gamma release assays and/or tuberculin-type skin tests. At least three subunit vaccine candidates containing ESAT6-like proteins as antigen components of multimeric proteins have shown efficacy in phase 1 and phase II clinical trials in humans.

Keywords: ESAT6-like proteins; M. tuberculosis; RD genomic segments; diagnosis; vaccine.

Figure 1

The organization of the CFP10 and ESAT6 genes in M. tuberculosis genome.