7ZQA

VelcroVax tandem HBcAg with SUMO-Affimer inserted at MIR (T=3* VLP)

Summary for 7ZQA

• Entry DOI: 10.2210/pdb7zqa/pdb
• Related: 7ZQ8
• EMDB information: 14868
• Descriptor: VelcroVax tandem HBcAg with SUMO-Affimer inserted at MIR (1 entity in total)
• Functional Keywords: velcrovax, hepatitis b virus, hepatitis b core antigen, affimer, vaccine, recombinant, vlp, antigen display, virus like particle
• Biological source: synthetic construct
• Total number of polymer chains: 18
• Total formula weight: 950269.86

Authors

Kingston, N.J.,Grehan, K.,Snowden, J.S.,Alzahrani, J.,Ranson, N.A.,Rowlands, D.J.,Stonehouse, N.J. (deposition date: 2022-04-29, release date: 2023-01-18, Last modification date: 2024-10-09)

Primary citation

Kingston, N.J.,Grehan, K.,Snowden, J.S.,Hassall, M.,Alzahrani, J.,Paesen, G.C.,Sherry, L.,Hayward, C.,Roe, A.,Stephen, S.,Tomlinson, D.,Zeltina, A.,Doores, K.J.,Ranson, N.A.,Stacey, M.,Page, M.,Rose, N.J.,Bowden, T.A.,Rowlands, D.J.,Stonehouse, N.J.
VelcroVax: a "Bolt-On" Vaccine Platform for Glycoprotein Display.
Msphere, 8:e0056822-e0056822, 2023

PubMed 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. 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.

PubMed: 36719225
DOI: 10.1128/msphere.00568-22

Experimental method

ELECTRON MICROSCOPY (3.6 Å)