Tuberculosis vaccines: current progress.

Tuberculosis continues to be a major cause of disease and death throughout the developing world. Chemotherapy is the current method of control but with the continuing emergence of drug resistance, coupled with the reticence of major drug companies to invest in drug discovery, the identification of new vaccines to combat tuberculosis is a pressing need. Rational vaccine design requires knowledge of the protective immune response and, while this is not fully understood, it is clear that induction of a T-helper-1 type of immunity is critical to host resistance. A variety of animal models, but especially the mouse and guinea pig, can be used to determine the protective efficacy of new vaccines. These mostly consist of relatively short-term prophylactic models in which animals are vaccinated and then challenged by the aerosol infection route to determine their capacity to reduce the lung bacterial load. Several promising vaccine types have emerged, including subunit vaccines, DNA vaccines and vaccines based upon living vectors, such as recombinant bacillus Calmette-Guérin (BCG) vaccines and auxotrophic or gene disrupted mutants of Mycobacterium tuberculosis. A few of these have already entered early stage clinical trials.