Currently antibody medicines require ultra-cold-chain during production and storage to prevent spoiling due to aggregation at the molecular level, which can occur at any stage from factory to patient. This project uses game-changing, proprietary Ensilication technology to remove this cold-chain dependence in the manufacturing and supply of antibody treatments. Ensilication technology will: * reduce product losses during manufacturing, * eliminate cold-chain costs and wastages during transport and storage. Additionally, there are potential patient benefits as ensilication supports antibody therapies to be reformulated for lower volume/higher concentration, allowing a move from intravenous to subcutaneous administration in the community/home rather than clinic settings. EnsiliTech and CPI will demonstrate the implementation of the Ensilication process for antibody production and will perform comprehensive analysis and comparison of COGS with ensilication addition. **Cold-chain logistics for antibody transport and storage** Most antibodies require cold-chain logistics, with most therapeutic antibodies needing ultra-cold storage (-80°C) due to their aggregation propensity. Cold-chain failures are expensive, costing the biopharmaceutical industry $35 billion annually. Cold-chain infrastructure is also challenging in low and middle-income countries (LMICs) making antibody treatments less accessible. **Antibody aggregation and easier subcutaneous administration** Antibodies are prone to aggregation, resulting in low product concentration and frozen storage. Most are administered intravenously in hospitals, inconveniencing patient experience with long injection times. Ensilication prevents antibody aggregation and allows for increased concentration in smaller volumes, which can enable reformulation for subcutaneous administration. This technology enhances ease of administration by reducing the physical volume of antibody treatments, removing aggregation and allowing for room-temperature stability. The project leverages the growing trend of reformulating intravenous antibody treatments for **subcutaneous administration**, which is less invasive, more convenient, and can be administered in community or home settings. **Impact of the Project** **Sustainability and Accessibility**: By removing the dependency on cold-chain logistics and improving antibody stability and administration, the project will significantly reduce costs and improve treatment access, especially in LMICs. **Scalability**: The manufacturing process developed for ensilicated antibodies is applicable to other products, creating a platform for the production of thermally-stable antibody therapies and other biopharmaceuticals. **Healthcare and Ecological Benefits**: The project reduces the environmental and economic burden of cold-chain logistics and hospital-based administration while improving patient access to advanced antibody therapies. Moving treatments to community settings will also alleviate pressure on healthcare systems. The intellectual property generated will be licensed to manufacturers, enabling sustainable production and broader distribution of antibody therapies across the globe.

EnsiliTech working with Afrigen and Emervax intend to develop a thermostable ensilicated messenger ribonucleic acid in lipid nanoparticle (mRNA-LNP) vaccine against the Hantaan virus (HTNV) that can be rapidly and equitably deployed globally. The Hantaan virus of the hantavirus family is predominantly present in Asia, although it occurs around the globe. It is transmitted through rodents, in this case the field mouse, as carriers to humans and causes haemorrhagic fever with renal syndrome (HFRS) that results in mortality up to 15% of infected individuals with yearly estimates of 200,000 cases globally. There is no vaccine commercially available. We believe that our combined effort and resources can contribute to the development of a safe, effective and modern vaccine against this virus. We strongly envision a world with equitable access to the latest vaccines that can prevent neglected infectious diseases. Emervax will provide their knowledge and experience in working on other Hantaviruses such as the Andes virus to the development of an mRNA cassette encoding the desired antigen. Afrigen will manufacture the drug substance (i.e. active pharmaceutical ingredient, API) and drug product which includes encapsulation within the LNP. EnsiliTech will investigate stabilisation of mRNA and mRNA-LNP using the ensilication technology, making it a room-temperature stable vaccine. This renders the cold chain logistics obsolete and increases accessibility and availability by extending shelf life and enhanced thermal stability. We believe this directly aligns with the scope and aims of the grant competition. We anticipated the results of this project to provide us with: * A novel antigenic mRNA construct efficacious against the HTNV demonstrated through _in vitro_ and _in vivo_ immunogenicity supported by challenge studies with subsequent first generation of mRNA-LNPs; * The establishment of mRNA-LNP ensilication and robust protocol thereof; * Thermostable vaccine formulation through ensilication; * Protective immunisation efficacy through intramuscular delivery _in vivo_ in rodents. The impact of the project would be the ability of this workflow to be templated on other neglected diseases and provide a platform for those emerging infectious pathogens such as Disease X. This project also addresses all key aspects towards the route to market for the final vaccine formulations. The created intellectual property (IP) will enable governmental bodies or non-governmental organisations to take a licence and support the manufacturing and distribution. Overall, our combined effort would intercalate and provide further opportunity for this consortium to become important contributors in the effort to improve global health.

Vaccines are known to be the most effective medical innovation in human history, credited with saving over 10 million lives since 1962\. The significant challenge with vaccines however is that they have to be kept refrigerated, between 2-8°C, at all times during their storage and transport, requiring a global infrastructure of refrigeration equipment known as the cold chain. This system is extremely costly to operate and prone to regular failures, the NHS reports almost 300,000 vaccines doses are wasted each year due to cold chain failures. Globally 1.5 million infants die each year from vaccine-preventable diseases, mainly in hot climates and low-middle income countries. Not only is this an issue with human vaccine distribution, but also with animal vaccines used in farming. In the UK, the British Veterinary Association estimates that only 27 % of vaccines administered by farmers are stored according to manufacturer guidelines. EnsiliTech has developed a novel technology to preserve vaccines, without the need for fridges and freezers at any point in their storage and distribution, called ensilication. The technology is highly scalable, using inexpensive materials and processes, making it easy to apply post-production. Ensilication aims to be applicable to most vaccines, allowing high degrees of protection against extremely low and high temperatures, high humidity, sunlight and acidity. The technology has been tested on a range of different biomolecules, ensuring that the vaccines will be fully protected and that there is no loss of efficacy in the protected vaccines. Over the course of the project, EnsiliTech will apply ensilication technology to relevant real world vaccines for diseases endemic to global animal populations. These are orally administered vaccines, reducing the use of needles and allowing more efficient vaccine administration and patient compliance. A thermally-stable oral tablet vaccine would revolutionise both the animal and human vaccine sectors, creating a new gold standard for vaccine preservation.