Comparative genomics of BCG vaccines by whole-genome DNA microarray

Bacille Calmette-Guerin (BCC) vaccines are live attenuated strains of Mycob acterium bovis administered to prevent tuberculosis. To better understand t he differences between M. tuberculosis, M. bovis, and the various BCC daugh ter strains, their genomic compositions were studied by performing comparat ive hybridization experiments on a DNA microarray. Regions deleted from BCG vaccines relative to the virulent M. tuberculosis H37Rv reference strain w ere confirmed by sequencing across the missing segment of the H37Rv genome. Eleven regions (encompassing 91 open reading frames) of H37Rv were found t hat were absent from one or more virulent strains of M. bovis. Five additio nal regions representing 38 open reading frames were present in M. bovis bu t absent from some or all BCC strains; this is evidence for the ongoing evo lution of BCG strains since their original derivation. A precise understand ing of the genetic differences between closely related Mycobacteria suggest s rational approaches to the design of improved diagnostics and vaccines.