二代测序法深度分析水痘疫苗Oka株病毒基因特征

采用二代测序(next-generation sequencing，NGS)技术，对上海生物制品研究所有限责任公司(简称SIBP)2015-2017这3个年度生产的Oka株水痘疫苗进行深度测序，从分子水平分析疫苗质量的一致性，并与不同厂家疫苗/毒种进行比较，分析它们之间的遗传特征相关性。结果显示，3个年度生产的水痘疫苗中平均有77个位点的疫苗型位点检出频率(proportion of vaccine-type allele，Pv)≥10%，至少在两批疫苗中出现Pv≥10%的位点数共76个，两两之间Pv最大差值<10%，与平均值的最大差值为<5%。共有40个位点的Pv均值≥30%，其中19个位点导致氨基酸残基变异；15个位于ORF62区域。筛选出35个位点，比较5个公司水痘疫苗/毒种的Oka株病毒基因序列，结果显示它们之间存在相关性，同时存在一定的差异。研究表明，SIBP不同年度生产的水痘疫苗Oka株病毒具有良好的分子水平上的一致性，为疫苗质量管理与市场监督提供了方法和基础数据。

Deep analysis of molecular characteristics of Oka strains of varicella vaccine with next-generation sequencing

Batches of Oka varicella vaccine prepared in different years by Shanghai Institute of Biological Products Co., Ltd. were deep-sequenced by the next-generation sequencing (NGS) technology and analyzed to evaluate the quality consistency in molecular level. In average there were 77 loci present in Oka genome with proportion of vaccine-type allele (Pv) no less than 10%, of which 76 appeared in at least two batches. The maximum Pv difference of batch-to-batch was less than 10%. There were 40 loci with average Pv no less than 30%, among which 19 led to amino acid changes and 15 located within ORF62 and adjacent non-coding area. The results demonstrate a good molecular consistency of Oka varicella vaccines produced in different years, and provide research methods and basic data for the quality control of vaccine manufacture and market supervision.