Vaccine Oka variants and sequence variability in vaccine-related skin lesions

As with most live attenuated viral vaccines, varicella vaccine comprises a mixture of variant strains. Knowledge about the pathogenic potential of individual strains in the varicella vaccine is limited. Vaccination against chickenpox causes a usually modified varicella-like rash in a small percentage of healthy children, and vaccine virus reactivates on rare occasions to cause herpes zoster (HZ). In several published studies, our respective laboratories have analyzed genomic variation among specimens from cases of postvaccination rash and HZ in vaccine recipients, focusing on polymorphisms between vaccine Oka strains and the parental Oka strain. In most respects, these studies were in close agreement, identifying the set of wild-type markers among vaccine adverse event isolates, each occurring at similar frequencies. The same 3 universally present vaccine markers, at positions 106262, 107252, and 108111, were also identified by both laboratories. One notable difference has been the observation of mostly clonal vaccine virus among isolates examined by one laboratory and mostly mixed viruses in isolates examined by the other. In addition to reviewing and comparing our combined observations, we propose possible explanations for our contrasting findings and propose future studies to reconcile them.