133428mAb manufacturing for future subunit vaccine platformClosedFeasibility StudiesISCFA platform for rapidly producing rationally engineered vaccines is urgently required to combat the threat of epidemic or pandemic pathogen outbreaks. Most existing vaccines are multicomponent products that are challenging to manufacture. The slowest step is typically transfer from preclinical proof-of-concept to GMP manufacture for human use. Manufacturing processes often require many product-specific steps precluding a standardised manufacturing platform. By contrast, advances made through significant and sustained investment into therapeutic monoclonal antibody (mAb) discovery and manufacture has made biosynthetic mass-production of high-yield, high-quality antibodies routine and broadly applicable, largely irrespective of the mAb's identity. We have exploited a protein engineering approach to vaccine development by combining target pathogen-specific proteins fused with the immunoglobulin heavy chain Fc domain. Fc fusion proteins are self-adjuvanting, targeting the antigen presenting cell through engagement with the Fc receptor. In this project we propose to combine state-of-the-art mAb manufacturing technology with several antigen-Fc fusion proteins, including some with novel modifications that increase potency, to assess the feasibility of a rapid and responsive "concept-to-human" platform for subunit vaccine discovery. A previous Innovate UK Biomedical Catalyst project has allowed us to apply our technology to MERS as a target pathogen. Targeting the major surface glycoprotein, S, we have produced several MERS candidate vaccines and shown good expression, purification and demonstrated immunogenicity in small mammals. Building on this we wish to address manufacturing possibilities that exploit the similarities between these Fc-containing candidates and traditional antibodies. By implication, successful application of mAb manufacturing to our current candidates should also apply to other targets suitable for Fc fusion technology making the routine rapid discovery and production of potent subunit vaccines using existing UK GMP therapeutic mAb facilities to protect against a range of known and emerging pathogens a realizable goal. Questions to be addressed include the yield of the product, its homogeneity, glycosylation status and oligomerisation, ease of purification and immunogenicity on a weight-to-weight basis, in comparison to established current materials. The project will combine the expertise of Anglo Biopharma, a British start-up biotechnology company focusing on rapid vaccine discovery for infections with unmet need, with Absolute Antibody, another British SME who are established leaders in rapid biosynthetic monoclonal antibody production. The third partner, the University of Reading, completes the team bringing experts in vaccine bioengineering and adjuvant formulation who will compare MERS subunit candidate vaccine produced by the new manufacturing process with existing material produced using current insect cell expression.