Decreased virulence of recombinant vaccinia virus expression vectors is associated with a thymidine kinase-negative phenotype

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Abstract
Recent advances in molecular genetics have led to the possibility of using large DNA viruses, such as vaccinia virus, as a biological delivery system for immunizing man against unrelated diseasecausing agents1–7. When live vaccinia virus recombinants expressing the hepatitis B virus surface antigen (HBsAg)8,9, the influenza A virus haemagglutinin10, the herpes simplex virus (HSV) type 1 D glycoprotein11,12, the rabies virus G glycoprotein13,14 and the vesicular stomatitis virus G glycoprotein15 were used for immunization, animals were protected upon challenge with the appropriate pathogenic agent. A major concern with using such vaccines, however, stems from the previously documented vaccinia virusassociated post-immunizing complications16. We present here experimental evidence that thymidine kinase-negative (TK−) vaccinia virus recombinants, constructed by inserting a variety of DNA coding sequences into the vaccinia virus tk gene, are less pathogenic for mice than wild-type virus.

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