972227Development of an economically viable CCHF virus vaccine for local productionClosedSmall Business Research InitiativeInnovate UKSome of the deadliest diseases we know about occur in areas of the world least well equipped to deal with them. The fact that they rarely cause problems in developed countries has hampered the production of preventative vaccines. Interest in these so called neglected diseases is limited owing to the small markets involved and poorly resourced healthcare. An example is Crimean Congo haemorrhagic fever (CCHF) virus, a severe disease that outbreaks sporadically in Africa, the Balkans, the Middle East and Asia. The virus is spread to humans via tick bites or contact with virus-infected animals, which rarely suffer disease, or other virus-infected humans. Flu-like symptoms develop within a week, with progression in 75% of cases to signs of haemorrhage including nosebleeds, vomiting and black stools. The liver becomes swollen and painful. Kidney function can also be affected with failure in the most severe cases. The mortality rate for the disease is 10-40%. One of the problems in developing such a vaccine is that as CCHF is so hazardous, any studies to produce a vaccine based on the intact virus must be conducted in specialized, high containment facilities. Although vaccines may be derived from inactivated, non-infectious CCHF virus, these have been shown to be toxic. An alternative approach is proposed in this project. We will use information about the genetics of CCHF virus to design a synthetic gene that has the code for making a protein component of the virus that in the course of an infection in humans results in the production of protective antibodies. This will be inserted into the DNA of an insect virus that is harmless to humans and because of other genetic modifications can no longer even infect its natural insect host. However, this modified virus can still be amplified in vats of insect cells grown in artificial nutrients. Simultaneously, it also produces the protein from CCHF virus. This can be isolated from the insect cells, purified and used subsequently in trials to determine if it is a suitable candidate for use as a vaccine. While initially producing the prototype CCHF virus vaccine is a complicated procedure, which requires a specialist laboratory-based facility, its subsequent use is not. All of the procedures necessary to use the prototype can be mimicked in a much simpler facility, using only basic scientific and production equipment. It is the aim of this project to develop CCHF virus vaccines that can be produced locally, where they are needed. The platform technology we develop will also be readily transferable to make vaccines for a number of other diseases related to CCHF virus that are likely to pose significant problems for human populations in the next few years.