Immunological requirements for a subunit vaccine against tuberculosis

Tuberculosis remains one of the most important threats to world health. Current vaccination and prevention strategies are inadequate and there is an urgent need for a new vaccine. The current vaccine bacille Calmette-Guerin (BCG), is unable to protect against re-activation of disease in later life and its efficacy varies tremendously in different human populations. An ideal replacement would be a non-living subunit vaccine that could impart protective efficacy greater than BCG but without its drawbacks. Before such a goal is achieved, however, there are many parameters that need to be examined in experimental systems. Such studies have revealed that apart from the selection of immunologically relevant antigens, dosage of antigen and type of adjuvant need to be chosen carefully. These parameters need to be examined in the context of the complex biology of the disease and, despite recent progress in defining host/pathogen interactions, experimental vaccines tested so far have fallen short of the protective efficacy of BCG. A coordinated approach, stimulating the various facets of cell-mediated immunity will probably be essential for development of protective immunity through subunit vaccination.