Production of an immunogenic trivalent poliovirus virus-like particle vaccine candidate in yeast using controlled fermentation
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.
Authors
- Suzanne Robb
- Jessica J. Swanson
- Sarah Carlyle (ORCID: https://orcid.org/0000-0002-7158-8134)
- Andrew Macadam (ORCID: https://orcid.org/0000-0002-8687-1573)
- Nicola J. Stonehouse (ORCID: https://orcid.org/0000-0003-1146-5519)
- David J. Rowlands (ORCID: https://orcid.org/0000-0002-4742-9272)
- Steven Wilkinson (ORCID: https://orcid.org/0000-0002-8075-4448)
- John Liddell
- Keith Grehan (ORCID: https://orcid.org/0000-0003-3976-756X)
- David I. Stuart (ORCID: https://orcid.org/0000-0002-3426-4210)
- Sue Matthews
- Lee Sherry (ORCID: https://orcid.org/0000-0002-4367-772X)
- Helen Fox (ORCID: https://orcid.org/0000-0002-5135-180X)
- Elizabeth E. Fry (ORCID: https://orcid.org/0000-0001-9754-5303)
- Nathaniel E. Clark (ORCID: https://orcid.org/0000-0002-5478-1610)
- Ling Qin (ORCID: https://orcid.org/0000-0001-7711-8371)
- Claudine Porta (ORCID: https://orcid.org/0000-0002-6788-4141)
- Mohammad W. Bahar
Institutions
- University of Leeds (GB)
- Centre for Human Genetics (GB)
- Diamond Light Source (GB)
- University of Oxford (GB)
Publication Details
- Journal
- npj Vaccines
- Published
- 2025-03-31
- DOI
- https://doi.org/10.1038/s41541-025-01111-2
- Citations
- 2
- Primary Topic
- Viral Infections and Immunology Research
- Type
- article
- Field-Weighted Citation Impact
- 2.78
Funders
- Engineering and Physical Sciences Research Council