[Strategies for the development of new tuberculosis vaccines]

Tuberculosis remains a substantial global health problem causing 2 million deaths, and an estimated 8 to 10 million new infections a year. The efficacy of the Mycobacterium bovis Bacillus Calmette-Guérin (BCG), the only available antituberculosis vaccine, is variable (0-80%), especially in tuberculosis-endemic countries. Over the past decade there has been a resurgence of interest in the development of new tuberculosis vaccines and some of the most promising are now entering into early clinical trials, based on two different strategies. The first is to use whole mycobacteria to replace BCG (priming vaccines), either by developing a recombinant strain of BCG or an attenuated strain of Mycobacterium tuberculosis. To date, two recombinant strains of BCG, one overexpressing antigen 85B (rBCG-85B) and the other, a urease-deficient BCG mutant which expresses the listeriolysin O gene from Listeria monocytogenes (rBCG::DeltaureC-hly+), entered into clinical trials. The second approach is to develop subunit vaccines (recombinant proteins and viral vectors, and DNA vaccines) expressing immunodominant antigen/s from M. tuberculosis able to augmenting BCG protection (booster vaccines). At the moment, three major vaccines, namely a recombinant modified vaccinia virus Ankara expressing antigen 85A (MVA85A), a fusion protein of ESAT6 and 85B (Hybrid 1), and another fusion protein comprising the 32 and 39 Kda proteins (72f) entered into clinical trials.