Recent progress in bacterial vaccines: Tuberculosis

AbstractBacille Calmette-Guérin (BCG) is the most widely used vaccine worldwide. However, its efficacy varies from 80% to zero among studies. Meta-analysis of all the published prospective trials and case-control studies indicates approximately 50% efficacy against all forms of tuberculosis, but it is even more effective against the invasive forms of the disease, meningitis and miliary tuberculosis. Geographic latitude accounts for 41% of the variance between studies. The variability between different BCG preparations and the role of environmental nontuberculous mycobacteria are discussed as mayor factors in the inconsistent results of BCG vaccine trials. New studies to define human genes that code for susceptibility to tuberculosis are reviewed. Despite the great strides being made in identifying vaccine candidates, there is still no reliable surrogate marker of protective immunity to tuberculosis. Human efficacy trials to document prevention of tuberculosis cannot possibly be mounted to test all the vaccine candidates that show promise in animal studies. Recent developments discussed include: the focus on secreted proteins of Mycobacterium tuberculosis as vaccine candidates, the genetic differences between BCG and virulent Mycobacterium bovis, the ability to create recombinant BCG-expressing cytokines that enhance the immune response and express vaccine candidate antigens, the availability of auxotrophic mutants of BCG as vaccine carriers, and the ongoing debate about other potential vaccine carriers, such as Salmonella, vaccinia (particularly modified vaccine Ankara [MVA]) and other avirulent pox viruses that do not replicate in humans