Sherry Lee, Grehan Keith, Bahar Mohammad W, Swanson Jessica J, Fox Helen, Matthews Sue, Carlyle Sarah, Qin Ling, Porta Claudine, Wilkinson Steven, Robb Suzanne, Clark Naomi, Liddell John, Fry Elizabeth E, Stuart David I, Macadam Andrew J, Rowlands David J, Stonehouse Nicola J
Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.
Division of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Headington, Oxford, OX3 7BN, UK.
NPJ Vaccines. 2025 Mar 31;10(1):64. doi: 10.1038/s41541-025-01111-2.
The success of the poliovirus (PV) vaccines has enabled the near-eradication of wild PV, however, their continued use post-eradication poses concerns, due to the potential for virus escape during vaccine manufacture. Recombinant virus-like particles (VLPs) that lack the viral genome remove this risk. Here, we demonstrate the production of PV VLPs for all three serotypes by controlled fermentation using Pichia pastoris. We determined the cryo-EM structure of a new PV2 mutant, termed SC5a, in comparison to PV2-SC6b VLPs described previously and investigated the immunogenicity of PV2-SC5a VLPs. Finally, a trivalent immunogenicity trial using bioreactor-derived VLPs of all three serotypes in the presence of Alhydrogel adjuvant, showed that these VLPs outperform the current IPV vaccine in the standard vaccine potency assay, offering the potential for dose-sparing. Overall, these results provide further evidence that yeast-produced VLPs have the potential to be a next-generation polio vaccine in a post-eradication world.
脊髓灰质炎病毒（PV）疫苗的成功已使野生PV近乎根除，然而，在根除后继续使用这些疫苗引发了担忧，因为在疫苗生产过程中存在病毒逃逸的可能性。缺乏病毒基因组的重组病毒样颗粒（VLP）消除了这种风险。在这里，我们展示了通过使用毕赤酵母进行受控发酵来生产所有三种血清型的PV VLP。与先前描述的PV2-SC6b VLP相比，我们确定了一种新的PV2突变体（称为SC5a）的冷冻电镜结构，并研究了PV2-SC5a VLP的免疫原性。最后，在存在氢氧化铝佐剂的情况下，使用所有三种血清型的生物反应器衍生VLP进行的三价免疫原性试验表明，这些VLP在标准疫苗效力测定中优于当前的灭活脊髓灰质炎疫苗（IPV），具有减少剂量的潜力。总体而言，这些结果进一步证明，在根除后的世界中，酵母产生的VLP有潜力成为下一代脊髓灰质炎疫苗。
