Grant: Project Grant

Crimean-Congo hemorrhagic fever virus (CCHFV) is the cause of a severe viral hemorrhagic fever that affects thousands across Asia, Africa, and parts of Europe. The disease is spread by bites from infected ticks, or by contact with the blood or body fluids of infected animals or individuals. The case-fatality can be as high as 40%, and even with medical attention there is significant chance of mortality. Risks for small or large-scale outbreaks include laboratory accidents, bioterrorism, and imported cases from countries where the disease is endemic, combined with the projected expansion of the niche of the ticks that carry the disease due to climate change. Moreover, individuals can remain asymptomatic for anywhere from 3-6 days, increasing the potential for the disease to spread as a result of travel. At present, our understanding of the disease is limited by the lack of suitable animal models that accurately mimic human disease. As no vaccine or post-exposure therapy exists for CCHFV, our proposal seeks to address these areas of need by a multifaceted approach. Specifically, the objectives of this proposal are the following: 1) Develop animal models of CCHFV pathogenesis and transmission, and test as systems for evaluating therapies. 2) Generate, through cloning, protective monoclonal antibodies from B-cells isolated from the convalescent plasma of CCHFV survivors, and validate these in our animal models. 3) Evaluate a DNA plasmid-based vaccine against CCHFV. This proposal will further our understanding of CCHFV, as our animal models will provide insights into transmission and pathogenesis, and will aid in the development of pre- and post-exposure therapies. Our group has an established track record of translational research that has lead to these types of therapies, currently under clinical evaluation. Collectively we anticipate that the findings from this study will have the potential to transform the way this disease is treated, and improve patient outcomes