Rabies in wildlife has been successfully controlled in parts of Europe and North America using oral rabies vaccination, i.e., the distribution of baits containing live-attenuated virus strains. Occasionally, these vaccines caused vaccine virus-induced rabies cases. To elucidate the mechanisms of genetic selection and the effect of viral populations on these rabies cases, a next generation sequencing approach as well as comprehensive data analyses of the genetic diversity of Street Alabama Dufferin (SAD) and ERA vaccine virus strains and vaccine-induced rabies cases from Canada and several European countries were conducted. As a result, twelve newly generated sets of sequencing data from Canada and Poland were added to a pool of previously investigated samples. While the population-based analysis showed a segregation of viruses of ERA vaccine-induced rabies cases from those of SAD Bern original (SAD Bernorig)-derived rabies cases, the in-depth variant analysis revealed three distinct combinations of selected variants for the ERA vaccine-induced cases, suggesting the presence of multiple replication-competent haplotypes in the investigated ERA-BHK21 vaccine. Our findings demonstrate the potential of a deep sequencing approach in combination with comprehensive analyses on the consensus, population, and variant level.

中文翻译：

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来自疫苗的狂犬病病毒的基于种群和变异的基因组分析证明了特定于产品的簇和独特的模式。

在欧洲和北美的部分地区，已经通过口服狂犬病疫苗接种成功地控制了野生动植物的狂犬病，即接种了含有减毒活病毒株的诱饵。这些疫苗有时会引起疫苗病毒引起的狂犬病病例。为了阐明遗传选择机制和病毒种群对这些狂犬病的影响，采用了下一代测序方法以及阿拉巴马州达弗林街（SAD）和ERA疫苗病毒株以及疫苗诱导的狂犬病的遗传多样性的综合数据分析来自加拿大和几个欧洲国家的案件进行了审理。结果，来自加拿大和波兰的十二个新生成的测序数据集被添加到先前调查的样本库中。虽然基于人群的分析显示ERA疫苗诱导的狂犬病病例的病毒与SAD伯尔尼原（SAD Bernorig）衍生的狂犬病病例的病毒分离，但深入的变体分析显示ERA疫苗所选变体的三种不同组合诱导的病例，表明在研究的ERA-BHK21疫苗中存在多种具有复制能力的单倍型。我们的研究结果表明，结合共识，总体和变异水平的综合分析，深度测序方法的潜力。提示在研究的ERA-BHK21疫苗中存在多种具有复制能力的单倍型。我们的研究结果表明，结合共识，总体和变异水平的综合分析，深度测序方法的潜力。提示在研究的ERA-BHK21疫苗中存在多种具有复制能力的单倍型。我们的研究结果表明，结合共识，总体和变异水平的综合分析，深度测序方法的潜力。