RECOMBINANT MYCOBACTERIAL EXPRESSION VEHICLES AND USES THEREFOR

摘要

Recombinant cultivable mycobacteria capable of expressing DNA of interest which encodes at least one protein antigen against which an immune response is desired and methods of introducing DNA of interest into mycobacteria. In the recombinant mycobacteria, the DNA of interest is stably maintained extrachromosomally or is stably integrated into genomic DNA. Such recombinant mycobacteria are useful as vehicles to be used as vaccines to provide immunity against a pathogen, as anti-fertility ''vaccines'' and as a means to nonspecifically augment immune responses to foreign antigens expressed by BCG or to treat human cancers. The present invention also relates to recombinant vectors useful in introducing DNA of interest into mycobacteria, where it is expressed. One type of vector is a recombinant plasmid capable of replicating as a plasmid in E. coli and of lyzogenizing a mycobacterial host. A second type of vector is a recombinant plasmid which can be introduced into mycobacteria, where it is stably maintained extrachromosomally. A third type of recombinant vector is one which replicates in E. coli but not in mycobacteria. It includes: 1) a mycobacterial gene, or portions thereof, necessary for recombination with homologous sequences in the genome of mycobacteria transformed with the recombinant plasmid; 2) all or a portion of a gene which encodes a polypeptide or protein whose expression is desired in mycobacteria transformed with the recombinant plasmid; 3) DNA sequences necessary for replication and selection in E. coli; and 4) DNA sequences necessary for selection in mycobacteria (e.g., drug resistance).