VelcroVax: a bolt-on vaccine platform technology improves antibody titres against a viral glycoprotein in mice

Stonehouse, N. J.; Kingston, N. J.; Grehan, K.; Snowden, J. S.; Hassall, M.; Alzahrani, J.; Paesen, G. C.; Sherry, L.; Hayward, C. R.; Roe, A.; Stephen, S.; Tomlinson, D. C.; Zeltina, A.; Doores, K. J.; Ranson, N. A.; Stacey, M.; Page, M.; Rose, N. J.; Bowden, T. A.; Rowlands, D. J.

doi:10.1101/2022.04.22.489148

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bioRxiv · 10.1101/2022.04.22.489148

VelcroVax: a bolt-on vaccine platform technology improves antibody titres against a viral glycoprotein in mice

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Abstract

Having varied approaches to the design and manufacture of vaccines is critical in being able to respond to worldwide needs and to newly emerging pathogens. Virus-like particle (VLP) vaccines 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 self-assemble into immunogenic nanoparticles. VLPs can also be modified to present unrelated antigens, and here we describe a universal bolt-on vaccine platform (termed VelcroVax) where the capturing VLP and the target antigen (hapten) are produced separately. We utilise 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 high-resolution structures of VelcroVax VLPs, and shown that the VelcroVax-JUNV gp1 complex induces superior humoral immune responses compared to the non-complexed viral protein. We propose that this system could be modified to present a range of haptens and therefore form the foundation of future rapid-response vaccination strategies.

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Stonehouse, N. J., Kingston, N. J., Grehan, K., Snowden, J. S., Hassall, M., Alzahrani, J., Paesen, G. C., Sherry, L., Hayward, C. R., Roe, A., Stephen, S., Tomlinson, D. C., Zeltina, A., Doores, K. J., Ranson, N. A., Stacey, M., Page, M., Rose, N. J., Bowden, T. A., Rowlands, D. J.. 2022-04-22. VelcroVax: a bolt-on vaccine platform technology improves antibody titres against a viral glycoprotein in mice. https://doi.org/10.1101/2022.04.22.489148

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