Moon Jae Yun, Seo Jina, Lee Jaewoo, Park Daechan
Department of Molecular Science and Technology, Ajou University, Suwon, South Korea.
Division of R&D Corporate Development, GC Biopharma, Yongin, South Korea.
J Med Virol. 2023 Mar;95(3):e28590. doi: 10.1002/jmv.28590.
Live attenuated varicella-zoster virus (VZV) vaccines are used to prevent chickenpox and shingles. Single nucleotide polymorphisms (SNPs) that occur during the attenuation of parental strains are critical indicators of vaccine safety. To assess the attenuation of commercial VZV vaccines, genetic variants were comprehensively examined through high-throughput sequencing of viral DNA isolated from four VZV vaccines (Barycela, VarilRix, VariVax, and SKY Varicella). Whole-genome comparison of the four vaccines with the wild-type strain (Dumas) revealed that the sequences are highly conserved on a genome-wide scale. Among the 196 common variants across the four vaccines, 195 were already present in the genome of the parental strain (pOka), indicating that the variants occurred during the generation of the parental strain from the Dumas strain. Compared to the pOka genome, the vaccines exhibited distinct variant frequencies on a genome-wide and within an attenuation-related open reading frame. In particular, attenuation-associated 42 SNPs showed that Barycela, VarilRix, VariVax, and SKY Varicella are in ascending order regarding similarity with pOka-like genotypes, which in turn, might provide genomic evidence for the levels of attenuation. Finally, the phylogenetic network analysis demonstrated that genetic distances from the parental strain correlated with the attenuation levels of the vaccines.
减毒活水痘 - 带状疱疹病毒（VZV）疫苗用于预防水痘和带状疱疹。亲代毒株减毒过程中出现的单核苷酸多态性（SNP）是疫苗安全性的关键指标。为评估市售VZV疫苗的减毒情况，通过对从四种VZV疫苗（Barycela、VarilRix、VariVax和SKY Varicella）中分离的病毒DNA进行高通量测序，全面检测了基因变异。将这四种疫苗与野生型毒株（Dumas）进行全基因组比较，结果显示这些序列在全基因组范围内高度保守。在这四种疫苗共有的196个常见变异中，有195个已存在于亲代毒株（pOka）的基因组中，这表明这些变异发生在从Dumas毒株产生亲代毒株的过程中。与pOka基因组相比，这些疫苗在全基因组范围以及与减毒相关的开放阅读框内表现出不同的变异频率。特别是，与减毒相关的42个SNP表明，Barycela、VarilRix、VariVax和SKY Varicella与pOka样基因型的相似性呈升序排列，这反过来可能为减毒水平提供基因组证据。最后，系统发育网络分析表明，与亲代毒株的遗传距离与疫苗的减毒水平相关。
