Bahar Mohammad W, Porta Claudine, Fox Helen, Macadam Andrew J, Fry Elizabeth E, Stuart David I
Division of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Headington, Oxford, OX3 7BN, UK.
The Pirbright Institute, Pirbright, Surrey, GU24 0NF, UK.
NPJ Vaccines. 2021 Jan 8;6(1):5. doi: 10.1038/s41541-020-00267-3.
Global vaccination programs using live-attenuated oral and inactivated polio vaccine (OPV and IPV) have almost eradicated poliovirus (PV) but these vaccines or their production pose significant risk in a polio-free world. Recombinant PV virus-like particles (VLPs), lacking the viral genome, represent safe next-generation vaccines, however their production requires optimisation. Here we present an efficient mammalian expression strategy producing good yields of wild-type PV VLPs for all three serotypes and a thermostabilised variant for PV3. Whilst the wild-type VLPs were predominantly in the non-native C-antigenic form, the thermostabilised PV3 VLPs adopted the native D-antigenic conformation eliciting neutralising antibody titres equivalent to the current IPV and were indistinguishable from natural empty particles by cryo-electron microscopy with a similar stabilising lipidic pocket-factor in the VP1 β-barrel. This factor may not be available in alternative expression systems, which may require synthetic pocket-binding factors. VLPs equivalent to these mammalian expressed thermostabilized particles, represent safer non-infectious vaccine candidates for the post-eradication era.
使用减毒口服活疫苗和灭活脊髓灰质炎疫苗（OPV和IPV）的全球疫苗接种计划几乎已根除脊髓灰质炎病毒（PV），但这些疫苗或其生产在无脊髓灰质炎的世界中带来了重大风险。缺乏病毒基因组的重组PV病毒样颗粒（VLP）代表了安全的下一代疫苗，然而其生产需要优化。在此，我们提出了一种高效的哺乳动物表达策略，可大量生产所有三种血清型的野生型PV VLP以及PV3的热稳定变体。虽然野生型VLP主要呈非天然的C抗原形式，但热稳定的PV3 VLP采用天然的D抗原构象，引发的中和抗体滴度与当前的IPV相当，并且通过冷冻电子显微镜观察，其与天然空颗粒难以区分，在VP1β桶中具有类似的稳定脂质口袋因子。在其他表达系统中可能没有这种因子，可能需要合成口袋结合因子。与这些哺乳动物表达的热稳定颗粒等效的VLP，代表了根除后时代更安全的非感染性候选疫苗。
