The BCG (bacille Calmette-Guérin) tuberculosis vaccine derived from Mycobacterium bovis emerged from serial passage of a virulent strain of M. bovis and offers limited protection against the disease. Comparative genomics has identified more than 100 sequences absent from BCG but present in M. tuberculosis, some of which may encode potential antigens that could improve immunogenicity if reintroduced into BCG. In the April 14 advanced online Nature Medicine, Alexander S. Pym and colleagues at the Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, Paris, France, show that recombinant BCG exporting the secreted T-cell antigens ESAT-6 (encoded in the region of deletion-1 (RD1) locus) confers enhanced protection against tuberculosis (DOI:10.1038/nm859, April 14, 2003).

Pym et al. created numerous BCG constructs containing the esxA and esxB genes, which encode ESAT-6 and CFP-10 respectively, and a variable number of flanking genes. They observed that only reintroduction of the complete RD1 locus, comprising...