摘要 |
The present invention relates to vaccines having an increased level of safety comprising recombinant vaccinia viruses. The invention also relates to methods for stimulating a protective immune response in an immunized host using the vaccines of the invention. The vaccines and recombinant vaccinia viruses of the invention comprise a first nucleic acid comprising and expression control sequence and a second nucleic acid comprising and exogenous nucleic acid encoding a conditional replication gene product, wherein the expression control sequence is operably linked to the exogenous nucleic acid. The exogenous nucleic acid may, by its expression or non-expression, confer upon the recombinant vaccinia virus either sensitivity or dependence upon an exogenous molecule (e.g. a drug) or a condition. Importantly, to allow the recombinant vaccinia viruses of the invention to replicate normally under permissive conditions, the exogenous nucleic acid is inserted into a non-essential locus (e.g. the E2L/E3L inter-genic locus, K1L/K2L inter-genic locus, the superoxide dismutase locus, and the 7.5K locus. |