Recent advances in improved tuberculosis vaccines.

Tuberculosis continues to be a major infectious cause of global morbidity and mortality, both in children and adults, in spite of widespread vaccination of infants with Bacille Calmette-Guerin (BCG) and the availability of effective antibiotics. The failure of BCG to significantly affect disease incidence in adults in many endemic countries, combined with the growing HIV epidemic and the appearance of multidrug resistant strains of Mycobacterium tuberculosis, threatens to overwhelm current tuberculosis control strategies. This unfortunate state of affairs has driven an intensive search for better tuberculosis vaccines. This article reviews the various vaccine development strategies which are being used e.g., purification or synthesis of protein peptide and non-peptide antigens from M. tuberculosis, creation of rationally-attenuated mutants of BCG and M. tuberculosis, development of DNA vaccines based upon the published genome sequence, the cloning of mycobacterial genes into living vaccine carrier strains (e.g., attenuated Salmonella, vaccinia virus, etc), or the use of naturally attenuated mycobacterial species (e.g., M. vaccae, M. microti). The animal models in which these vaccine candidates are being screened for protective efficacy (e.g., the mouse, guinea pig, rabbit, primate) will be discussed briefly. Finally, some of the challenges inherent in the eventual clinical evaluation of new tuberculosis vaccines are reviewed.