Attenuation and laboratory markers of the Oka-strain varicella-zoster virus.

A live varicella vaccine was developed by serial passages of the Oka-strain varicella-zoster virus (VZV), isolated in our laboratory, in human embryonic lung cells and guinea-pig embryonic fibroblasts (GPEF). It is slightly temperature sensitive at 39 degrees C and shows a higher ratio of infectivity in GPEF to that in human embryonic fibroblasts (HuEF) than wild-type strains, indicating that it is a variant in thermosensitivity and host dependency. A DNA digest with the HpaI enzyme of the Oka strain contained a unique fragment, denoted K. Clinical studies with VZV isolated from vaccinees indicated that the GPEF/HuEF ratio of infectivity and the profiles of HpaI DNA digests are useful tests to differentiate the vaccine from wild-type strains. Prompt vaccination of household contacts proved effective in preventing spread of clinical varicella and seemed to be related to the early appearance (4-7 days after vaccination) of cell-mediated immunity in vaccinees, assessed by the VZV skin test. VZV could be isolated from mononuclear blood cells of varicella patients shortly before or after appearance of rashes, whereas no virus could be detected in 27 vaccinees 4-14 days after vaccination, suggesting that replication of the vaccine virus in susceptible organs and blood cells in humans is far less than that of wild-type viruses, but sufficient to induce VZV immunity. This difference seems to be related to the attenuated nature of the vaccine strain.