Recombinant expression systems for production of stabilised virus-like particles as next-generation polio vaccines
Abstract Polioviruses have caused crippling disease in humans for centuries, prior to the successful development of vaccines in the mid-1900’s, which dramatically reduced disease prevalence. Continued use of these vaccines, however, threatens ultimate disease eradication and achievement of a polio-f...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56118-z |
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| author | Lee Sherry Mohammad W. Bahar Claudine Porta Helen Fox Keith Grehan Veronica Nasta Helen M. E. Duyvesteyn Luigi De Colibus Johanna Marsian Inga Murdoch Daniel Ponndorf Seong-Ryong Kim Sachin Shah Sarah Carlyle Jessica J. Swanson Sue Matthews Clare Nicol George P. Lomonossoff Andrew J. Macadam Elizabeth E. Fry David I. Stuart Nicola J. Stonehouse David J. Rowlands |
| author_facet | Lee Sherry Mohammad W. Bahar Claudine Porta Helen Fox Keith Grehan Veronica Nasta Helen M. E. Duyvesteyn Luigi De Colibus Johanna Marsian Inga Murdoch Daniel Ponndorf Seong-Ryong Kim Sachin Shah Sarah Carlyle Jessica J. Swanson Sue Matthews Clare Nicol George P. Lomonossoff Andrew J. Macadam Elizabeth E. Fry David I. Stuart Nicola J. Stonehouse David J. Rowlands |
| author_sort | Lee Sherry |
| collection | DOAJ |
| description | Abstract Polioviruses have caused crippling disease in humans for centuries, prior to the successful development of vaccines in the mid-1900’s, which dramatically reduced disease prevalence. Continued use of these vaccines, however, threatens ultimate disease eradication and achievement of a polio-free world. Virus-like particles (VLPs) that lack a viral genome represent a safer potential vaccine, although they require particle stabilization. Using our previously established genetic techniques to stabilize the structural capsid proteins, we demonstrate production of poliovirus VLPs of all three serotypes, from four different recombinant expression systems. We compare the antigenicity, thermostability and immunogenicity of these stabilized VLPs against the current inactivated polio vaccine, demonstrating equivalent or superior immunogenicity in female Wistar rats. Structural analyses of these recombinant VLPs provide a rational understanding of the stabilizing mutations and the role of potential excipients. Collectively, we have established these poliovirus stabilized VLPs as viable next-generation vaccine candidates for the future. |
| format | Article |
| id | doaj-art-e79f680974a94b2ca77c3e7a16ce8072 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e79f680974a94b2ca77c3e7a16ce80722025-01-19T12:30:54ZengNature PortfolioNature Communications2041-17232025-01-0116111710.1038/s41467-025-56118-zRecombinant expression systems for production of stabilised virus-like particles as next-generation polio vaccinesLee Sherry0Mohammad W. Bahar1Claudine Porta2Helen Fox3Keith Grehan4Veronica Nasta5Helen M. E. Duyvesteyn6Luigi De Colibus7Johanna Marsian8Inga Murdoch9Daniel Ponndorf10Seong-Ryong Kim11Sachin Shah12Sarah Carlyle13Jessica J. Swanson14Sue Matthews15Clare Nicol16George P. Lomonossoff17Andrew J. Macadam18Elizabeth E. Fry19David I. Stuart20Nicola J. Stonehouse21David J. Rowlands22Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of LeedsDivision of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic MedicineDivision of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic MedicineDivision of Vaccines, Medicines & Healthcare products Regulatory Agency (MHRA)Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of LeedsDivision of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic MedicineDivision of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic MedicineDivision of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic MedicineJohn Innes Centre, Norwich Research ParkJohn Innes Centre, Norwich Research ParkJohn Innes Centre, Norwich Research ParkJohn Innes Centre, Norwich Research ParkJohn Innes Centre, Norwich Research ParkDivision of Vaccines, Medicines & Healthcare products Regulatory Agency (MHRA)Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of LeedsAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of LeedsAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of LeedsJohn Innes Centre, Norwich Research ParkDivision of Vaccines, Medicines & Healthcare products Regulatory Agency (MHRA)Division of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic MedicineDivision of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic MedicineAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of LeedsAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of LeedsAbstract Polioviruses have caused crippling disease in humans for centuries, prior to the successful development of vaccines in the mid-1900’s, which dramatically reduced disease prevalence. Continued use of these vaccines, however, threatens ultimate disease eradication and achievement of a polio-free world. Virus-like particles (VLPs) that lack a viral genome represent a safer potential vaccine, although they require particle stabilization. Using our previously established genetic techniques to stabilize the structural capsid proteins, we demonstrate production of poliovirus VLPs of all three serotypes, from four different recombinant expression systems. We compare the antigenicity, thermostability and immunogenicity of these stabilized VLPs against the current inactivated polio vaccine, demonstrating equivalent or superior immunogenicity in female Wistar rats. Structural analyses of these recombinant VLPs provide a rational understanding of the stabilizing mutations and the role of potential excipients. Collectively, we have established these poliovirus stabilized VLPs as viable next-generation vaccine candidates for the future.https://doi.org/10.1038/s41467-025-56118-z |
| spellingShingle | Lee Sherry Mohammad W. Bahar Claudine Porta Helen Fox Keith Grehan Veronica Nasta Helen M. E. Duyvesteyn Luigi De Colibus Johanna Marsian Inga Murdoch Daniel Ponndorf Seong-Ryong Kim Sachin Shah Sarah Carlyle Jessica J. Swanson Sue Matthews Clare Nicol George P. Lomonossoff Andrew J. Macadam Elizabeth E. Fry David I. Stuart Nicola J. Stonehouse David J. Rowlands Recombinant expression systems for production of stabilised virus-like particles as next-generation polio vaccines Nature Communications |
| title | Recombinant expression systems for production of stabilised virus-like particles as next-generation polio vaccines |
| title_full | Recombinant expression systems for production of stabilised virus-like particles as next-generation polio vaccines |
| title_fullStr | Recombinant expression systems for production of stabilised virus-like particles as next-generation polio vaccines |
| title_full_unstemmed | Recombinant expression systems for production of stabilised virus-like particles as next-generation polio vaccines |
| title_short | Recombinant expression systems for production of stabilised virus-like particles as next-generation polio vaccines |
| title_sort | recombinant expression systems for production of stabilised virus like particles as next generation polio vaccines |
| url | https://doi.org/10.1038/s41467-025-56118-z |
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