Commercialisation of a therapeutic bacterial vesicle engineering and manufacturing platform

Bacteria naturally release portions of their cell membrane. These outer membrane vesicles (OMVs) are essentially tiny molecular packages containing proteins, fats and other molecules. Bacteria use OMVs to communicate with other cells and to transfer molecules. OMVs are also attractive for use as vaccines or as vehicles for delivering drugs and other therapeutic agents because of their ability to interact with host cells and their natural immunogenic properties. OMV vaccines for use in humans include GSK’s Bexsero®, a Neisseria meningitidis vaccine, that has received MHRA, EMA and US FDA approval and has achieved sales of £218m in Q1 of 2023 alone. Future OMV-based animal vaccines are also likely to have economic and food security importance, or as an exemplar, could help to protect the broiler industry from losing significant numbers of chickens each year due to avian pathogenic E. coli (APEC) related diseases. Further to this, APEC isolates have genetic similarities in terms of virulence markers, with human uropathogenic E. coli (UPEC), and as such may have zoonotic potentials. Worryingly, some APEC strains have also been reported to be resistant to all classes of antibiotics. It may therefore, become increasingly desirable for OMV-based cross protective vaccines to be developed to protect against UPEC and/or APEC in poultry and humans. However, whilst OMV vaccines and therapeutics are promising, our engagements with industry have highlighted important challenges. For example, OMV vaccine manufacturing is typically non-standardised and requires the culture of weakened or highly infectious bacteria to generate the relevant vaccine antigens. Furthermore, the custom engineering of each new bacterial strain to ensure commercially viable OMV yields can slow down OMV vaccine development. Additionally, widely used OMV isolation methods during the manufacturing process might not produce OMVs at suitable yields, purity or bioactivities required for specific applications. Further advancements in OMV engineering approaches are also desirable to enable the manufacture of OMVs with novel therapeutic modalities to treat additional animal or human diseases. To help accelerate next generation OMV therapeutics we have developed an Outer Membrane vEsicle enGineering and mAnufacturing (OMEGA) platform technology to create better and scalable methods for manufacturing new kinds of vaccine or therapeutic OMVs. Our approach differentiates itself from competing technologies through the way in which we have specially engineered our OMEGA bacterial strains to help make it easier to biomanufacture many kinds of therapeutic OMVs in a modular or "Lego-like" fashion. Importantly, our approach also incorporates methods that help simplify our OMV manufacturing process making it easier to produce and isolate OMVs at larger scales. BBSRC FoF support will be used to further scale our OMV manufacturing platform technology, strengthen OMEGA IP, and to carry out focused comparative studies that derisk and show the competitiveness of our approach. Importantly, we will also develop a panel of OMV R&D products and candidate OMV-based APEC vaccines that alongside our continued engagement with the EV industry and other stakeholders will help us to shape and expedite a responsible translational pathway for OMEGA-OMV vaccine and therapeutic manufacturing for the future benefit of animal and human health.