Department of Pathology.
J Infect Dis. 2014 Feb 1;209(3):334-44. doi: 10.1093/infdis/jit546. Epub 2013 Oct 17.
The first comparison of a live RNA viral vaccine strain to its wild-type parental strain by deep sequencing is presented using as a model the yellow fever virus (YFV) live vaccine strain 17D-204 and its wild-type parental strain, Asibi.
The YFV 17D-204 vaccine genome was compared to that of the parental strain Asibi by massively parallel methods. Variability was compared on multiple scales of the viral genomes. A modeled exploration of small-frequency variants was performed to reconstruct plausible regions of mutational plasticity.
Overt quasispecies diversity is a feature of the parental strain, whereas the live vaccine strain lacks diversity according to multiple independent measurements. A lack of attenuating mutations in the Asibi population relative to that of 17D-204 was observed, demonstrating that the vaccine strain was derived by discrete mutation of Asibi and not by selection of genomes in the wild-type population.
Relative quasispecies structure is a plausible correlate of attenuation for live viral vaccines. Analyses such as these of attenuated viruses improve our understanding of the molecular basis of vaccine attenuation and provide critical information on the stability of live vaccines and the risk of reversion to virulence.
首次通过深度测序对活 RNA 病毒疫苗株与其野生型亲本株进行比较，以黄热病毒（YFV）活疫苗株 17D-204 及其野生型亲本株 Asibi 为模型进行了介绍。
通过大规模平行方法比较 YFV 17D-204 疫苗基因组与亲本株 Asibi 的基因组。在病毒基因组的多个尺度上比较了变异性。对小频率变异进行了模型探索，以重建可能的突变可塑性区域。
明显的准种多样性是亲本株的特征，而活疫苗株根据多种独立测量缺乏多样性。与 17D-204 相比，Asibi 群体中缺乏减毒突变，表明疫苗株是由 Asibi 的离散突变产生的，而不是由野生型群体中基因组的选择产生的。
相对准种结构是活病毒疫苗减毒的合理相关因素。对减毒病毒的此类分析可提高我们对疫苗减毒分子基础的理解，并提供有关活疫苗稳定性和毒力恢复风险的关键信息。
