Deep Sequencing of Distinct Preparations of the Live Attenuated Varicella-Zoster Virus Vaccine Reveals a Conserved Core of Attenuating Single-Nucleotide Polymorphisms.
Deep Sequencing of Distinct Preparations of the Live Attenuated Varicella-Zoster Virus Vaccine Reveals a Conserved Core of Attenuating Single-Nucleotide Polymorphisms.
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DOI：
10.1128/jvi.00998-16
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发表时间：
2016-10-01
影响因子：
5.4
通讯作者：
Breuer J
中科院分区：
文献类型：
--
作者：
Depledge DP;Yamanishi K;Gomi Y;Gershon AA;Breuer J
减毒水痘带状疱疹病毒活疫苗在预防水痘带状疱疹和带状疱疹方面的持续成功已有充分记录，许多导致沃卡病毒在皮肤中复制减毒的突变也是如此。至少有三种不同的 vOka 制剂已上市。在这里，我们使用来自三个不同制造商（VariVax、GSK 和 Biken）的七批 vOka 疫苗（包括 ZostaVax、VariVax、VariRix 和 Oka/Biken 工作种子）的深度测序显示，所有疫苗批次中都存在 137 个单核苷酸多态性 (SNP) 突变。这包括疫苗等位基因固定或接近固定的六个位点，我们推测这可能对减毒很重要。我们还表明，尽管制剂之间的疫苗群体存在差异，但批次之间的差异很小，各个批次特有的突变数量和频率也是如此。这表明疫苗生产过程没有引入新的突变，并且尽管存在多种变体，VZV 活疫苗仍然非常稳定。重要性 预防水痘和带状疱疹的疫苗接种持续取得成功，加上不良反应发生率极低，表明了这些疫苗的质量。疫苗本身由异质减毒活病毒群组成，因此需要深度测序技术来探索不同制剂和批次疫苗之间病毒群的差异和相似性。我们的数据表明批次之间的差异很小，这是一个重要的安全特征，并为这种减毒病毒中存在的突变程度提供了新的见解。
The continued success of the live attenuated varicella-zoster virus vaccine in preventing varicella-zoster 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 single-nucleotide polymorphism (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 also 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 that, notwithstanding the mixture of variants present, VZV live vaccines are extremely stable. IMPORTANCE The continued success of vaccinations to prevent chickenpox and shingles, combined with the extremely low incidence of adverse reactions, indicates the quality of these vaccines. The vaccine itself is comprised of a heterogeneous live attenuated virus population and thus requires deep-sequencing technologies to explore the differences and similarities in the virus populations between different preparations and batches of the vaccines. Our data demonstrate minimal variation between batches, an important safety feature, and provide new insights into the extent of the mutations present in this attenuated virus.