VelcroVax : a "Bolt-On" Vaccine Platform for Glycoprotein Display
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
mSphere - 8(2023), 1 vom: 21. Feb., Seite e0056822 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kingston, Natalie J [VerfasserIn] |
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| Links: |
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| Themen: |
Glycoproteins |
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| Anmerkungen: |
Date Completed 23.02.2023 Date Revised 09.03.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1128/msphere.00568-22 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM352296054 |
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| 520 | |a 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 | ||
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| 700 | 1 | |a Hassall, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Alzahrani, Jehad |e verfasserin |4 aut | |
| 700 | 1 | |a Paesen, Guido C |e verfasserin |4 aut | |
| 700 | 1 | |a Sherry, Lee |e verfasserin |4 aut | |
| 700 | 1 | |a Hayward, Connor |e verfasserin |4 aut | |
| 700 | 1 | |a Roe, Amy |e verfasserin |4 aut | |
| 700 | 1 | |a Stephen, Sam |e verfasserin |4 aut | |
| 700 | 1 | |a Tomlinson, Darren |e verfasserin |4 aut | |
| 700 | 1 | |a Zeltina, Antra |e verfasserin |4 aut | |
| 700 | 1 | |a Doores, Katie J |e verfasserin |4 aut | |
| 700 | 1 | |a Ranson, Neil A |e verfasserin |4 aut | |
| 700 | 1 | |a Stacey, Martin |e verfasserin |4 aut | |
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| 700 | 1 | |a Rose, Nicola J |e verfasserin |4 aut | |
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| 700 | 1 | |a Rowlands, David J |e verfasserin |4 aut | |
| 700 | 1 | |a Stonehouse, Nicola J |e verfasserin |4 aut | |
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