10026700The Protein ForgeClosedSmall Business Research InitiativeInnovate UKThe ideal vaccine is safe, effective and adapted to low-income countries (i.e., cheap and easy to manufacture, store and administer). These features are difficult to combine and strongly affected by delivery platforms (the way the vaccine is made and presented to the immune system). Trusted delivery platforms that can easily be adapted to fit a new disease are crucial to preparedness for 'disease X', the as yet unknown pathogen that will bring the next pandemic. This project is the first step towards one such platform. Newly developed vaccines are based on platforms such as RNA/DNA, viruses, and subunit scaffolds (engineered nanoparticles or virus-like-particles). Each of these approaches has distinct advantages and disadvantages: there is unlikely to be a "one-size-fits-all" vaccine platform that addresses pathogens as diverse as the Covid-19 virus, the TB bacterium, and the malaria parasite. Increasing the diversity of delivery platforms strengthens our hand against real global threats: antibiotic resistance, the evolution of new variants, and the transfer of diseases from another species to our own. Against this danger, this project will exploit our existing nanotechnology which has many characteristics of a potent platform. It provides a scaffold for the active ingredient of a vaccine and presents it to the immune system in a highly effective way. Recent reviews herald engineered nanoparticles as opening a new era in the rational design of effective vaccines. There is good reason to think that ours is amongst the most promising. We anticipate that our platform will be both flexible and effective and this research is the first stage of demonstrating its potential. In it, we aim to produce early-stage candidate vaccines against a variety of globally significant pathogens. Success will trigger collaborative work with vaccine specialists to test the safety and effectiveness of these candidates, first in the laboratory and then in humans. The history of research into vaccines is one of many failures and a few outstanding successes. Choosing the wrong platform leads researchers to blind alleys and delays vaccine development. Our work packages will demonstrate our platform's potential, engage our partners and meet the urgent need for platform choice. The rewards of success remain very great. A platform that allows the creation or enhancement of even just one key vaccine has the potential to save thousands or even millions of lives.