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
{"title":"用于生产作为下一代脊髓灰质炎疫苗的稳定病毒样颗粒的重组表达系统","authors":"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","doi":"10.1038/s41467-025-56118-z","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"20 1","pages":""},"PeriodicalIF":15.7000,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Recombinant expression systems for production of stabilised virus-like particles as next-generation polio vaccines\",\"authors\":\"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\",\"doi\":\"10.1038/s41467-025-56118-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>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.</p>\",\"PeriodicalId\":19066,\"journal\":{\"name\":\"Nature Communications\",\"volume\":\"20 1\",\"pages\":\"\"},\"PeriodicalIF\":15.7000,\"publicationDate\":\"2025-01-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Communications\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1038/s41467-025-56118-z\",\"RegionNum\":1,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Communications","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41467-025-56118-z","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
Recombinant expression systems for production of stabilised virus-like particles as next-generation polio vaccines
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.
期刊介绍:
Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.