New vaccines for the prevention of tuberculosis

Mycobacterium bovis, bacille Calmette-Guérin (BCG) is administered widely to newborns throughout the world and has been shown to be effective in preventing childhood tuberculosis but not reactivation pulmonary disease or human immunodeficiency virus-associated tuberculosis. Development of a more effective, better standardized, affordable vaccine with durable activity and fewer side effects is a major priority. Contemporary molecular techniques have identified promising immunodominant antigens and novel immunization strategies. Vaccine development has also been informed by an improved understanding of the role of nontuberculous mycobacteria in the efficacy of BCG and in the prevention of tuberculosis. Vaccines under investigation include attenuated or enhanced whole-cell live, whole-cell inactivated, subunit, DNA, and prime-boost vaccines. Several candidate vaccines have demonstrated activity in animal models that is equal to or superior to that of BCG, and human trials are under way. Because there is no identified surrogate marker for protection, identification of an improved vaccine will require long-term efficacy trials in humans.