[Search for new tuberculosis vaccines].

Studies in animal models and analysis of human genetic defects leading to severe mycobacteriosis, establish the major role of cellular immune responses in the control of tuberculosis. The BCG vaccine protects infants against severe forms of tuberculosis (meningitis and miliary tuberculosis). However its protective efficacy against the adult forms of tuberculosis is highly variable, ranging from 0% to 90% in different vaccine trials. Different attempts are being made to isolate new vaccines. Protein antigens exported by Mycobacterium tuberculosis provide some level of protection when delivered as recombinant protein antigens or as DNA vaccines. Attenuated strains of M. tuberculosis are obtained by targetted inactivation of a variety of genetic involved in virulence. Their potential as new live vaccine is being studied. In addition a single mutation at the purC locus inactivating the purine biosynthetic pathway was shown to result in dramatic attenuation. The purC M. tuberculosis mutant strain provided protection against an aerosol challenge in guinea pigs. Future protocoles for vaccination against tuberculosis may include new attenuated strains with multiple well characterised mutations and a series of exported antigens.