Recombinant expression systems for production of stabilised virus-like particles as next-generation polio vaccines

Lee Sherry, Mohammad W. Bahar, Claudine Porta, Helen Fox, Keith Grehan, Veronica Nasta, Helen M. E. Duyvesteyn, Luigi 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 () and David J. Rowlands ()
Additional contact information
Lee Sherry: University of Leeds
Mohammad W. Bahar: The Henry Wellcome Building for Genomic Medicine
Claudine Porta: The Henry Wellcome Building for Genomic Medicine
Helen Fox: Medicines & Healthcare products Regulatory Agency (MHRA)
Keith Grehan: University of Leeds
Veronica Nasta: The Henry Wellcome Building for Genomic Medicine
Helen M. E. Duyvesteyn: The Henry Wellcome Building for Genomic Medicine
Luigi Colibus: The Henry Wellcome Building for Genomic Medicine
Johanna Marsian: John Innes Centre, Norwich Research Park
Inga Murdoch: John Innes Centre, Norwich Research Park
Daniel Ponndorf: John Innes Centre, Norwich Research Park
Seong-Ryong Kim: John Innes Centre, Norwich Research Park
Sachin Shah: John Innes Centre, Norwich Research Park
Sarah Carlyle: Medicines & Healthcare products Regulatory Agency (MHRA)
Jessica J. Swanson: University of Leeds
Sue Matthews: University of Leeds
Clare Nicol: University of Leeds
George P. Lomonossoff: John Innes Centre, Norwich Research Park
Andrew J. Macadam: Medicines & Healthcare products Regulatory Agency (MHRA)
Elizabeth E. Fry: The Henry Wellcome Building for Genomic Medicine
David I. Stuart: The Henry Wellcome Building for Genomic Medicine
Nicola J. Stonehouse: University of Leeds
David J. Rowlands: University of Leeds

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-56118-z

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