VelcroVax: a “Bolt-On” Vaccine Platform for Glycoprotein Display
ABSTRACT Having varied approaches to the design and manufacture of vaccines is critical in being able to respond to worldwide needs and newly emerging pathogens. Virus-like particles (VLPs) form the basis of two of the most successful licensed vaccines (against hepatitis B virus [HBV] and human papi...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2023-02-01
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| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/msphere.00568-22 |
| _version_ | 1828010545088823296 |
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| author | Natalie J. Kingston Keith Grehan Joseph S. Snowden Mark Hassall Jehad Alzahrani Guido C. Paesen Lee Sherry Connor Hayward Amy Roe Sam Stephen Darren Tomlinson Antra Zeltina Katie J. Doores Neil A. Ranson Martin Stacey Mark Page Nicola J. Rose Thomas A. Bowden David J. Rowlands Nicola J. Stonehouse |
| author_facet | Natalie J. Kingston Keith Grehan Joseph S. Snowden Mark Hassall Jehad Alzahrani Guido C. Paesen Lee Sherry Connor Hayward Amy Roe Sam Stephen Darren Tomlinson Antra Zeltina Katie J. Doores Neil A. Ranson Martin Stacey Mark Page Nicola J. Rose Thomas A. Bowden David J. Rowlands Nicola J. Stonehouse |
| author_sort | Natalie J. Kingston |
| collection | DOAJ |
| description | ABSTRACT Having varied approaches to the design and manufacture of vaccines is critical in being able to respond to worldwide needs and newly emerging pathogens. Virus-like particles (VLPs) form the basis of two of the most successful licensed vaccines (against hepatitis B virus [HBV] and human papillomavirus). They are produced by recombinant expression of viral structural proteins, which assemble into immunogenic nanoparticles. VLPs can be modified to present unrelated antigens, and here we describe a universal “bolt-on” platform (termed VelcroVax) where the capturing VLP and the target antigen are produced separately. We utilize a modified HBV core (HBcAg) VLP with surface expression of a high-affinity binding sequence (Affimer) directed against a SUMO tag and use this to capture SUMO-tagged gp1 glycoprotein from the arenavirus Junín virus (JUNV). Using this model system, we have solved the first high-resolution structures of VelcroVax VLPs and shown that the VelcroVax-JUNV gp1 complex induces superior humoral immune responses compared to the noncomplexed viral protein. We propose that this system could be modified to present a range of antigens and therefore form the foundation of future rapid-response vaccination strategies. IMPORTANCE The hepatitis B core protein (HBc) forms noninfectious virus-like particles, which can be modified to present a capturing molecule, allowing suitably tagged antigens to be bound on their surface. This system can be adapted and provides the foundation for a universal “bolt-on” vaccine platform (termed VelcroVax) that can be easily and rapidly modified to generate nanoparticle vaccine candidates. |
| first_indexed | 2024-04-10T09:01:26Z |
| format | Article |
| id | doaj.art-b7c301ef9e3a4446bd7a97505024123b |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-04-10T09:01:26Z |
| publishDate | 2023-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-b7c301ef9e3a4446bd7a97505024123b2023-02-21T14:03:57ZengAmerican Society for MicrobiologymSphere2379-50422023-02-018110.1128/msphere.00568-22VelcroVax: a “Bolt-On” Vaccine Platform for Glycoprotein DisplayNatalie J. Kingston0Keith Grehan1Joseph S. Snowden2Mark Hassall3Jehad Alzahrani4Guido C. Paesen5Lee Sherry6Connor Hayward7Amy Roe8Sam Stephen9Darren Tomlinson10Antra Zeltina11Katie J. Doores12Neil A. Ranson13Martin Stacey14Mark Page15Nicola J. Rose16Thomas A. Bowden17David J. Rowlands18Nicola J. Stonehouse19Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United KingdomAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United KingdomAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United KingdomDivision of Virology, National Institute for Biological Standards and Control (NIBSC), Hertfordshire, United KingdomAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United KingdomDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Oxford, United KingdomAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United KingdomAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United KingdomAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United KingdomAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United KingdomAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United KingdomDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Oxford, United KingdomDepartment of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, United KingdomAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United KingdomAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United KingdomDivision of Virology, National Institute for Biological Standards and Control (NIBSC), Hertfordshire, United KingdomDivision of Virology, National Institute for Biological Standards and Control (NIBSC), Hertfordshire, United KingdomDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Oxford, United KingdomAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United KingdomAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United KingdomABSTRACT Having varied approaches to the design and manufacture of vaccines is critical in being able to respond to worldwide needs and newly emerging pathogens. Virus-like particles (VLPs) form the basis of two of the most successful licensed vaccines (against hepatitis B virus [HBV] and human papillomavirus). They are produced by recombinant expression of viral structural proteins, which assemble into immunogenic nanoparticles. VLPs can be modified to present unrelated antigens, and here we describe a universal “bolt-on” platform (termed VelcroVax) where the capturing VLP and the target antigen are produced separately. We utilize a modified HBV core (HBcAg) VLP with surface expression of a high-affinity binding sequence (Affimer) directed against a SUMO tag and use this to capture SUMO-tagged gp1 glycoprotein from the arenavirus Junín virus (JUNV). Using this model system, we have solved the first high-resolution structures of VelcroVax VLPs and shown that the VelcroVax-JUNV gp1 complex induces superior humoral immune responses compared to the noncomplexed viral protein. We propose that this system could be modified to present a range of antigens and therefore form the foundation of future rapid-response vaccination strategies. IMPORTANCE The hepatitis B core protein (HBc) forms noninfectious virus-like particles, which can be modified to present a capturing molecule, allowing suitably tagged antigens to be bound on their surface. This system can be adapted and provides the foundation for a universal “bolt-on” vaccine platform (termed VelcroVax) that can be easily and rapidly modified to generate nanoparticle vaccine candidates.https://journals.asm.org/doi/10.1128/msphere.00568-22HBcAgVLPJunín virusplatformvaccine |
| spellingShingle | Natalie J. Kingston Keith Grehan Joseph S. Snowden Mark Hassall Jehad Alzahrani Guido C. Paesen Lee Sherry Connor Hayward Amy Roe Sam Stephen Darren Tomlinson Antra Zeltina Katie J. Doores Neil A. Ranson Martin Stacey Mark Page Nicola J. Rose Thomas A. Bowden David J. Rowlands Nicola J. Stonehouse VelcroVax: a “Bolt-On” Vaccine Platform for Glycoprotein Display mSphere HBcAg VLP Junín virus platform vaccine |
| title | VelcroVax: a “Bolt-On” Vaccine Platform for Glycoprotein Display |
| title_full | VelcroVax: a “Bolt-On” Vaccine Platform for Glycoprotein Display |
| title_fullStr | VelcroVax: a “Bolt-On” Vaccine Platform for Glycoprotein Display |
| title_full_unstemmed | VelcroVax: a “Bolt-On” Vaccine Platform for Glycoprotein Display |
| title_short | VelcroVax: a “Bolt-On” Vaccine Platform for Glycoprotein Display |
| title_sort | velcrovax a bolt on vaccine platform for glycoprotein display |
| topic | HBcAg VLP Junín virus platform vaccine |
| url | https://journals.asm.org/doi/10.1128/msphere.00568-22 |
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