Knowlson Sarah, Burlison John, Giles Elaine, Fox Helen, Macadam Andrew J, Minor Philip D
Division of Virology, National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, United Kingdom.
PLoS Pathog. 2015 Dec 31;11(12):e1005316. doi: 10.1371/journal.ppat.1005316. eCollection 2015 Dec.
Poliomyelitis has nearly been eradicated through the efforts of the World Health Organization's Global Eradication Initiative raising questions on containment of the virus after it has been eliminated in the wild. Most manufacture of inactivated polio vaccines currently requires the growth of large amounts of highly virulent poliovirus, and release from a production facility after eradication could be disastrous; WHO have therefore recommended the use of the attenuated Sabin strains for production as a safer option although it is recognised that they can revert to a transmissible paralytic form. We have exploited the understanding of the molecular virology of the Sabin vaccine strains to design viruses that are extremely genetically stable and hyperattenuated. The viruses are based on the type 3 Sabin vaccine strain and have been genetically modified in domain V of the 5' non-coding region by changing base pairs to produce a cassette into which capsid regions of other serotypes have been introduced. The viruses give satisfactory yields of antigenically and immunogenically correct viruses in culture, are without measurable neurovirulence and fail to infect non-human primates under conditions where the Sabin strains will do so.
通过世界卫生组织全球根除脊髓灰质炎行动的努力，脊髓灰质炎几乎已被根除，这引发了在该病毒在自然界中被消灭后如何控制它的问题。目前，大多数灭活脊髓灰质炎疫苗的生产需要培养大量高致病性脊髓灰质炎病毒，而在根除后从生产设施中释放这些病毒可能会带来灾难性后果；因此，世卫组织建议使用减毒的萨宾毒株进行生产，认为这是一个更安全的选择，尽管人们认识到它们可能会回复到可传播的麻痹形式。我们利用对萨宾疫苗株分子病毒学的认识，设计出了遗传上极其稳定且高度减毒的病毒。这些病毒基于3型萨宾疫苗株，通过改变碱基对在5'非编码区的V结构域进行了基因改造，以产生一个盒式结构，其他血清型的衣壳区域已被引入该盒式结构中。这些病毒在培养中能产生抗原性和免疫原性正确的病毒，产量令人满意，没有可测量的神经毒性，并且在萨宾毒株能够感染非人类灵长类动物的条件下，它们无法感染非人类灵长类动物。
