Tuberculosis (TB) is still an important infectious disease throughout the world. Early diagnosis and treatment of TB is difficult, vaccination is the most effective way in prevention.Bacille Calmette-Guérin (BCG), an attenuated vaccine derived from Mycobacterium bovis, is the current vaccine of choice against tuberculosis (TB).

The attenuation process during vaccine development promoted certain genomic deletions, that together with the evolution of M. bovis, resulted in 16 different genomic regions (RD1–RD16, plus nRD18), when compared with the Mtb genome. Therefore, over the years sub-strains of BCG has emerged. These strains are distributed throughout the world and the main concern is that such strains can not provide reliable protection against TB. This situation is taken into consideration in the vaccine studies. Although BCG has high efficacy in protecting children from severe forms of TB, the overall protection conferred by BCG varies between 0 and 80%. There is a significant effort towards the development of a new TB vaccine.

This review is focused on BCG vaccines and new TB vaccine approaches such as genetically modified BCG, vaccines against the protein antigen (Ag85, p65, ESAT-6), recombinant subunit vaccines, carbohydrate conjugate vaccines, mucosal vaccines and therapeutic vaccines.

Much progress has been made in the effort to improve vaccination against TB, with some promising candidates, but considerable work is still required to address prevention of TB. These new approaches should be evaluated in human models to prove that the vaccine is effective and safe in TB prevention.