BCG, a live attenuated strain of Mycobacterium bovis, offers a number of distinct advantages as a live recombinant vaccine vehicle. These advantages include potent adjuvant activity and a history of safe use in humans as a tuberculosis vaccine. Major genetic obstacles impeding the development of BCG as a vaccine vehicle have now been largely overcome with the development of Escherichia coli/mycobacterial shuttle vectors. Recent immunogenicity studies with several recombinant BCG-based vaccines are promising and suggest that high-level expression of the target antigen may contribute to its antigen immunodominance in the complex background of mycobacterial proteins. Since it has been observed that constitutive high- level expression of some foreign antigens in BCG is deleterious to the BCG host strain, we propose to develop a BCG vector/host system incorporating BCG stress promotors with transcriptional components from bacteriophage T7 (T7 RNA polymerase) and the E. coli lactose operon (Lac repressor and operator) to regulate the high-level synthesis of recombinant antigens in BCG. In addition to providing an inexpensive source of antigen in an immunogenic format without antigen purification, it is also possible that the proposed BCG/T7 system could provide an alternative to live recombinant BCG vaccines which might not be suitable in immunocompromised individuals.
