Decreased virulence of recombinant vaccinia virus expression vectors is associated with a thymidine kinase-negative phenotype.
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 disease-causing agents. When live vaccinia virus recombinants expressing the hepatitis B virus surface antigen (HBsAg), the influenza A virus haemagglutinin, the herpes simplex virus (HSV) type 1 D glycoprotein, the rabies virus G glycoprotein and the vesicular stomatitis virus G glycoprotein 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 virus-associated post-immunizing complications. 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.
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D004274:DNA, Recombinant; D005822:Genetic Vectors; D007928:Lethal Dose 50; D008099:Liver / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D010641:Phenotype; D013154:Spleen / Q000382:microbiology; D013937:Thymidine Kinase / Q000235:genetics / Q000502:physiology*; D014611:Vaccination; D014615:Vaccinia / Q000382:microbiology; D014616:Vaccinia virus / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D014765:Viral Vaccines; D014774:Virulence; D014779:Virus Replication
D000914:Antibodies, Viral; D004274:DNA, Recombinant; D014765:Viral Vaccines; D013937:Thymidine Kinase