Improved Q Fever Vaccine (DSTL, PHE, ICENI DX & Mologic)

Virus-like particles (VLPs) are a flexible delivery platform that provides potential for presenting multiple antigens to the immune system concurrently. Hepatitis B core antigen self assembles to form highly stable, immunogenic VLPs in a relatively low cost yeast expression system. The viral protein can be adapted to display foreign antigens on spikes that protrude from the surface of the VLPs. This technology circumvents the need for high cost, high containment production facilities, cold transportation and storage. Our goal is to produce a cost effective, second generation Q fever vaccine, using VLP technology as a production platform. In initial proof of concept studies, the Mologic-Dstl-Iceni Diagnostics consortium has successfully produced and tested Burkholderia pseudomallei vaccine candidates based on yeast-produced VLPs presenting either peptide or polysaccharide antigens. These candidates were efficacious in a mouse model of Melioidosis, demonstrating the readiness of this technology for roll out for antibacterial vaccine production. In the current proposal, we will consolidate and extend our work on this platform, applying it to Coxiella burnetii, the causative agent of Q Fever, which is listed as an agent of concern by the WHO and UN. Q fever is found worldwide and there is high prevalence in low income countries. This VLP platform bid will draw on expertise in Coxiella burnetii antigenicity to develop a vaccine against Q fever. It has been shown that C. burnetii lipopolysaccharide (LPS) provides protection against challenge, indicating that it is a key protective antigen. LPS itself is a T-cell independent antigen; conjugation to a protein carrier can improve antibody isotype development and crucially stimulate B cell memory. Therefore, to increase vaccine efficacy and develop immune memory to Coxiella, we propose conjugating native C. burnetii LPS, or synthetic fragments thereof, to VLP carriers. In parallel, we will express previously identified C. burnetii protein surface antigens on VLPs, providing material for potential blending with LPS-VLP conjugates to produce multi-antigen vaccines. The novel VLP vaccines produced in this study will be tested in our established mouse model of C. burnetii aerosol infection; immune responses will be determined and related to the vaccine efficacy. Several VLP vaccines have already been licensed for human use, demonstrating an established path to market. The opportunity to manufacture without high level containment will result in inexpensive vaccines where manufacture can be transferred to low income settings. This will serve to pave the way for future development of low-cost vaccines for other globally significant pathogens.