Modified Mycobacterium offers new TB vaccine platform

A modified Mycobacterium smegmatis bacterial strain expressing a secretion system encoded by genes from Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis, has a potent ability to protect mice from infection with Mtb. The findings, published online this week in Nature Medicine, may yield useful new tools for development of a candidate vaccine against Mtb. The locus for the esx-3 gene cluster is essential for Mtb survival, but not for M. smegmatis. William Jacobs, Jr. and colleagues show that the Mtb esx-3 genes can replace the similar genes in M. smegmatis, inducing propagation of protective CD4+ T immune cells in mice injected with the hybrid (or new strain of) M. smegmatis. The CD4+ T cell-dependent immunity against subsequent exposure to Mtb was as good as or better than that induced by BCG, the only vaccine against Mtb in current use. The authors note that further studies are needed to elucidate the mechanisms by which replacement of the esx-3 locus in M. smegmatis generates a vaccine strain capable of inducing robust clearance of Mtb in the mice.