Deep-sequencing of distinct preparations of the live-attenuated VZV vaccine reveals a conserved core of attenuating SNPs

The continued success of the live-attenuated varicella zoster virus vaccine in preventing varicella and herpes zoster is well documented, as are many of the mutations that contribute to the attenuation of the vOka virus for replication in skin. At least three different preparations of vOKa are marketed. Here, we show using deep sequencing of seven batches of vOka vaccine (including ZostaVax, VariVax, VarilRix and the Oka/Biken working seed) from three different manufacturers (VariVax, GSK and Biken) that 137 SNP mutations are present in all vaccine batches. This includes six sites at which the vaccine allele is fixed or near-fixation which we speculate are likely to be important for attenuation. We additionally show that despite differences in the vaccine populations between preparations, batch to batch variation is minimal, as is the number and frequency of mutations unique to individual batches. This suggests that the vaccine manufacturing processes are not introducing new mutations and notwithstanding the mixture of variants present, VZV live vaccines are extremely stable.