Tuberculosis: new strategies for the development of diagnostic tests and vaccines.

New diagnostic tests and vaccines for tuberculosis are being developed by means of a strategy based on the study of antigens exclusive to Mycobacterium tuberculosis. These antigens were initially identified by Western blots using sera from active pulmonary tuberculosis patients against sonic extracts from M. tuberculosis and M. bovis BCG. Several proteins present in the M. tuberculosis but absent in the Mycobacterium bovis BCG sonic extracts were selected and are currently under investigation. One of these, denoted MTP40, has been extensively studied. The nucleotide sequence of the mtp40 gene has been obtained; hybridization studies have shown that this DNA fragment is exclusive to M. tuberculosis. Using this genomic fragment, a polymerase chain reaction (PCR)-based diagnostic test which allows the specific identification of a minimum of 10 fg of M. tuberculosis DNA was developed. The diagnostic assay is now being tested on uncultured clinical samples in order to determine its usefulness in routine diagnosis. Peptides synthesized from the derived sequence for the MTP40 protein and also from other M. tuberculosis proteins are now being studied as possible candidates for a new generation of synthetic vaccines against tuberculosis.