7zq8
VelcroVax tandem HBcAg with SUMO-Affimer inserted at MIR (T=4 VLP)
Structural highlights
Publication Abstract from PubMedHaving 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 Junin 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. VelcroVax: a "Bolt-On" Vaccine Platform for Glycoprotein Display.,Kingston NJ, Grehan K, Snowden JS, Hassall M, Alzahrani J, Paesen GC, Sherry L, Hayward C, Roe A, Stephen S, Tomlinson D, Zeltina A, Doores KJ, Ranson NA, Stacey M, Page M, Rose NJ, Bowden TA, Rowlands DJ, Stonehouse NJ mSphere. 2023 Feb 21;8(1):e0056822. doi: 10.1128/msphere.00568-22. Epub 2023 Jan , 31. PMID:36719225[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
