HSV-1 thymidine kinase negative vaccine: pathogenicity, protection, and perils.
Primary inoculation of mice and rabbits with an avirulent HSV-1 thymidine kinase negative (TK-) mutant reduced keratitis, mortality, and superinfection of the trigeminal ganglion (TG) as measured by cocultivation and iontophoresis-induced ocular shedding following ocular challenge with HSV-1 McKrae and W strains. However species differences were demonstrated; with complete protection in rabbits, and incomplete protection in mice. In mice, BUDR/autoradiography and restriction enzyme analysis identified both HSV-1 McKrae and W strains as having superinfected the TG, established latency and reactivated. Also, the avirulent TK negative inoculating strain was altered to a virulent TK positive strain through possible in vivo selection, mutation &/or host-modification, and possible in vivo recombination with the virulent challenge strains. We conclude that lower species differences require that potential HSV-1 vaccines be tested in non-human primates prior to clinical trials, and that a DNA-free subunit herpes vaccine represents a safer alternative to a live virus vaccine.
D000818:Animals; D007635:Keratitis, Dendritic / Q000382:microbiology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D013937:Thymidine Kinase / Q000235:genetics*; D014765:Viral Vaccines / Q000627:therapeutic use*
D014765:Viral Vaccines; D013937:Thymidine Kinase