Fox Helen, Knowlson Sarah, Minor Philip D, Macadam Andrew J
Division of Virology, National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, United Kingdom.
PLoS Pathog. 2017 Jan 19;13(1):e1006117. doi: 10.1371/journal.ppat.1006117. eCollection 2017 Jan.
While wild type polio has been nearly eradicated there will be a need to continue immunisation programmes for some time because of the possibility of re-emergence and the existence of long term excreters of poliovirus. All vaccines in current use depend on growth of virus and most of the non-replicating (inactivated) vaccines involve wild type viruses known to cause poliomyelitis. The attenuated vaccine strains involved in the eradication programme have been used to develop new inactivated vaccines as production is thought safer. However it is known that the Sabin vaccine strains are genetically unstable and can revert to a virulent transmissible form. A possible solution to the need for virus growth would be to generate empty viral capsids by recombinant technology, but hitherto such particles are so unstable as to be unusable. We report here the genetic manipulation of the virus to generate stable empty capsids for all three serotypes. The particles are shown to be extremely stable and to generate high levels of protective antibodies in animal models.
虽然野生型脊髓灰质炎已几乎被根除,但由于脊髓灰质炎有重新出现的可能性以及存在长期排出脊髓灰质炎病毒的情况,在一段时间内仍需要继续开展免疫计划。目前使用的所有疫苗都依赖病毒生长,并且大多数非复制型(灭活)疫苗都涉及已知会导致小儿麻痹症的野生型病毒。根除计划中使用的减毒疫苗株已被用于开发新的灭活疫苗,因为人们认为其生产更安全。然而,已知萨宾疫苗株基因不稳定,可能会回复到有传染性的致病形式。解决病毒生长需求的一个可能办法是通过重组技术生成空病毒衣壳,但迄今为止,此类颗粒非常不稳定,无法使用。我们在此报告对病毒进行基因操作以生成针对所有三种血清型的稳定空衣壳。这些颗粒显示出极其稳定,并在动物模型中产生高水平的保护性抗体。