Comparative genomics of BCG vaccines.

Bacille Calmette-Guérin (BCG) vaccines have been given to more people than any other vaccine. They have also probably resulted in as much controversy as any other vaccine. In clinical trials, the efficacy of BCG vaccination against pulmonary TB has been widely variable. At the same time, a number of investigators have observed phenotypic differences between BCG daughter strains, raising the possibility that differences between BCG products may in some way translate into different outcomes. With recent genomic analysis of BCG strains, it has become possible to piece together the molecular events that have resulted in current BCG vaccines. Between the derivation of BCG in 1921 and the lyophilization of BCG Pasteur 1173 in 1961, there have been at least seven genetic events, including deletions, duplications and a single nucleotide polymorphism. The phenotypic relevance of these changes in BCG vaccines remains to be explored.