Development of a subunit vaccine against CCHF virus for use in low-middle income countries; completion of pre-clinical studies

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Crimean Congo Haemorrhagic Fever virus (CCHFv) is the most widespread tick-borne viral disease affecting people. It is endemic in \>30 countries, almost all of which are LMICs in Africa, the Balkans, Middle East and Central Asia with an estimated 3 billion people at risk. The expanding geographic range of the tick along with trade in infected but asymptomatic livestock is fuelling the spread of CCHFv. Virus outbreaks occur in agricultural areas in workers with close contact with animals, spreading to family members and health workers. Thus CCHFv affects regions and countries least able to deal with CCHFv or afford vaccine development. There is no vaccine, nor effective treatment; early intensive care, rehydration and supportive drug therapy are the main care pathways. There are 10-15,000 cases annually; 1 in 8 develop severe disease with mortality rates between 10 and 40% (WHO). Survivors typically experience long term debilitating symptoms that have additional socio-economic impacts.Our project aims to develop a safe, affordable and effective vaccine for CCHFv using our platform technologies for producing high quality proteins, including viral glycoproteins, in insect cells. This project will build on the results and achievements of our current UK Vaccine Network project and ensure we are well prepared and ready to move to Phase I/II Clinical Trials in future.In this 1 year project, we will finalise the adjuvant to be used with the vaccine, which ensures a good immune response and protection. The aim is to achieve protection after an initial and one booster dose. Current tests of vaccine performance depend on the use of an animal model in high containment facilities to assess protection from the virus. We will develop an alternative approach that is animal-free and utilizes a cell culture-based method performed in lower containment laboratories. This will enable effective but more affordable assessment of vaccine efficacy/immune response in future Clinical Phases of vaccine development. We will also optimize stability of the vaccine, which currently can be preserved for 1 month in a refrigerator. Based on work with a prototype COVID-19 vaccine produced in the same system we think this can be improved to 3 to 6 months. This will reduce the burden of cold chain supply in LMICs. Finally, we will create a regulatory package and develop a detailed plan to undertake Phase I/Phase II Trials to allow future Clinical work packages to start as soon as funding is available.