Genomic comparison reveals single-nucleotide polymorphic sites and attenuation-associated site combinations specific to Chinese live attenuated varicella-zoster virus vaccines

The live-attenuated varicella-zoster virus (VZV) vaccine, mainly based on the Oka strain, is essential for the prevention and control of chickenpox (varicella). Although genomic profiles of internationally prevalent Oka vaccine strain (vOka)-derived preparations have been reported, the comprehensive single-nucleotide polymorphism (SNP) profiles of multiple commercially available Chinese vOka-derived vaccines are still lacking. We performed next-generation sequencing (NGS) on five Chinese-manufactured VZV vaccines, comparing genomic variations against the wild-type parental Oka (pOka) strain and internationally prevalent vaccine products. Notably, among 54 key SNPs distinguishing Chinese vaccines from the wild-type pOka strain, 4 novel China-specific SNPs were identified. What's more, we identified 6 near-fixed (the vaccine allele frequency >90%) non-synonymous SNPs that consistently co-occurred across all production batches, potentially impacting protein function through amino acid substitutions. Genetic heterogeneity across manufacturers revealed manufacturer-specific signatures, whereas consistent batch production underscored manufacturing stability. By systematically mapping SNPs in Chinese VZV vaccines, this study bridges a critical knowledge gap and provides essential insights into manufacturer-specific genomic signatures.