‘Plug and Display’ Virus-like Particle Platform for Rapid Response Vaccination Response Vaccination

Virus-like particles (VLP) are a platform technology that are used to produce vaccines against many different diseases. These technologies are particularly suited for the induction of strong antibody responses, which they achieve through presentation of an ordered antigen array to the immune system. Many different types of VLP vaccine have been tested in preclinical studies and some licensed vaccines employ this technology, such as the hepatitis B vaccine. The Jenner Institute and Biochemistry Department at the University of Oxford have recently established a platform VLP vaccine technology for irreversibly decorating VLPs simply by mixing with protein antigen in a "plug-and-display" manner. Critically, this approach overcomes the well-described challenges of producing VLP carriers with complex antigens genetically-fused on their surface, or low conjugation efficiency often reported when using chemical conjugation. In this project we will generate VLP vaccines that display key target antigen from outbreak viral pathogens. In order to do this, we will make use of the novel SpyCatcher-SpyTag technology platform to 'plug-and-display' target antigens on the VLPs. This technology allows for the rapid and efficient formation of a spontaneous isopeptide bond (irreversible linking) between the small SpyCatcher (10 kDa) on the VLP carrier surface and a short versatile 13 amino acid SpyTag incorporated within the antigen. This strategy is versatile and particularly useful for rapidly generating VLP vaccines to emerging and outbreak pathogens of public health concern. We will initially generate a universal VLP carrier that can be utilised for this technology platform. In parallel we will express the Ebola, Marburg, Zika and Chikungunya virus glycoproteins fused to SpyTag, fuse them to the VLP carrier, and test the immunogencity and in vitro immuno-efficacy providing comparison wherever possible to other leading technologies. We also provide proof-of-concept using a second Tag-Catcher system, that bivalent vaccines targeting two related pathogens, e.g. Ebola and Marburgh, can also be rapidly and easily generated. Once this platform technology is established, the universal VLP carrier will be available for display of antigens identified from future outbreak or emerging pathogens. Once the carrier platform is produced to cGMP, rapid vaccine production will simply rely on the expression of SpyTagged antigen relevant to the outbreak pathogen and rapid irreversible fusion to the VLP carrier. This technology platform will provide a rapid route to production of a final one-component VLP vaccine that is highly immunogenic and suited for single or repeated homologous immunisation.