Inducible and repressible vaccinia viruses with improved safety

A recombinant vaccinia virus comprising:

• a first recombinant nucleic acid comprising a tet response element and a nucleic acid encoding a conditional replication gene product, wherein the tet response element is operably linked to the nucleic acid encoding the conditional replication gene product;
• and
• a second recombinant nucleic acid comprising an expression control sequence and a nucleic acid encoding a tet repressor or a reverse tet repressor that conditionally binds the tet response element, wherein the expression control sequence is operably linked to the nucleic acid encoding the tet repressor or a reverse tet repressor, and wherein the second recombinant nucleic acid is located in a non-essential region of the vaccinia virus genome or in an intergenic region of the vaccinia virus genome, and
• wherein the conditional replication gene product is a gene product that is toxic to a mammalian host or cells, lowers the fitness of the recombinant vaccinia virus, or interferes with the replication of VACV, and
• wherein expression of the conditional replication gene product is inducible or repressible by a tetracycline antibiotic.