Kingston, NJ, Grehan, K orcid.org/0000-0003-3976-756X, Snowden, JS et al. (17 more authors) (2023) VelcroVax: a ‘bolt-on’ vaccine platform for glycoprotein display. mSphere, 8 (1). e0056822. ISSN 2379-5042
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 Kingston et al. This is an open access article published under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | HBcAg, VLP, Junín virus, platform, vaccine |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Cryo EM, Image Processing (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Molecular Virology (Leeds) |
Funding Information: | Funder Grant number MRC (Medical Research Council) MR/P022626/1 National Institute of Health - NIH (PHS) Not Known |
Depositing User: | Symplectic Publications |
Date Deposited: | 21 Dec 2022 12:35 |
Last Modified: | 25 Jun 2023 23:11 |
Status: | Published |
Publisher: | American Society for Microbiology |
Identification Number: | 10.1128/msphere.00568-22 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:194460 |
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Licence: CC-BY 4.0