An evaluation of single nucleotide polymorphisms used to differentiate vaccine and wild type strains of varicella‐zoster virus

Rashes following immunization with the vaccine strain (vOka) of varicella-zoster virus (VZV) may occur in up to 5% of children and 10% of adults. In 40% of cases, the causative virus is the vaccine strain and in 60% wild type virus is found. Several reports have identified three restriction site polymorphisms in ORF 62 and the loss of one in ORF 6, which differentiate vOka from wild type VZV, including the parental wild type strain from which vOka, is derived. Using polymerase chain reaction (PCR), restriction enzyme analysis, and sequencing, we analyzed the presence of these markers in the GlaxoSmithKline (GSK, UK) and Merck vaccine preparations as well as in 15 vaccine virus rashes and 15 wild type UK viruses. Our data suggest that a Sma1 positive and an Nae1 positive site in ORF 62 are present in the GSK and Merck vaccine preparations and all vaccine virus rashes. By contrast, a BssHII positive vaccine virus restriction site in ORF 62 and an Alu1 negative site in ORF 6 were mixed in the GSK and Merck vaccines and absent in some of the vaccine rashes. The BssHII site was also present in the European wild type C viruses in UK. The data suggest that unlike the Biken vaccine preparation, the Merck and GSK vaccine preparations are polymorphic for the BssHII and Alu1 restriction sites. These sites are also present variably in the vaccine viruses causing rashes following vaccination, and are therefore unreliable markers for differentiating vOka and wild type VZV strains.