Development of an economically viable CCHF virus vaccine

Crimean-Congo Haemorrhagic Fever (CCHF) is a serious virus (v) disease primarily transmitted to humans by ticks. The mortality rate is up to 40% with survivors experiencing long term debilitating health problems that have socio-economic impact at all levels. Incidences of the disease are increasing, with outbreaks across much of sub-Saharan Africa, large parts of Asia, Southern Russia and the Arabian Peninsula. There have been cases in Spain and Greece with CCHF endemic in Turkey. The expanding geographic range of the tick host along with trade in infected but nonsymptomatic livestock is fuelling the spread of CCHF. There is no vaccine currently available so public health measures are the only options to prevent virus spread. Virus outbreaks most often occur in agricultural areas in workers who have had close contact with animals, spreading to family members. Thus CCHF, along with some of the world’s other deadliest diseases, affects areas least able to deal with them or afford to develop vaccines. These diseases rarely cause problems in developed countries so there has hitherto been little interest in the development of preventative vaccines, although CCHF is now knocking on the door of Western Europe. Commercial interest in these so called neglected diseases is limited owing to the relatively small and intermittent markets. A further problem in developing a vaccine for CCHFv is that it is hazardous to work with, and so research to produce a vaccine based on the intact virus must be conducted in specialized, high containment facilities. Vaccines may be derived from inactivated, non-infectious CCHFv, but these have been shown to be toxic. We propose an alternative approach, which is based on successful pilot work we carried out over the past year. We used information about the genetics of CCHFv to design synthetic genes for making protein components of the virus outer coat that during an infection in humans should result in the production of a protective immune response. In this project we will optimise production of our candidate vaccine using an innovative, safe insect virus vector produced in insect cells that are easy to grow to a scale in simple culture vessels. We will fully characterise the properties of the vaccine and carry out initial safety and potency tests to facilitate future clinical trials. We will also optimise vaccine production to achieve stable material over a range of temperatures to minimise reliance on cold chain supply in target countries. While initially producing the prototype CCHFv vaccine is a complicated procedure, which requires a specialist laboratory-based facilities, 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 therefore an associated aim of our project to develop a CCHFv vaccine that could be produced locally, for example in emergency outbreak situations. The platform technology we develop will also be readily transferable to make vaccines for a number of other diseases similar to CCHFv that already, or are likely to, pose significant problems for human populations in the next few years. An added advantage of our insect production system is the ability to respond quickly to emerging threats - we can move from gene to protein/vaccine in as little as eight weeks.