Cooperative mechanisms of innate and adaptive immune responses targeting hepatitis C virus infection

• Applicant: Dr. Florian Wrensch
• Subject Area: Virology
• Term: from 2018 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 395783133

Acute hepatitis C virus (HCV) infection leads to persistent infection in the majority of infected subjects. Chronic HCV infection can progress to chronic hepatitis, cirrhosis and and hepatocellular carcinoma. Yet in a subset of acutely infected subjects, infection is self-limited leading to spontaneous viral clearance. While several studies have demonstrated evidence that neutralizing antibodies contribute to control of and protection against viral infection, the role non-neutralizing antibodies with Fc-mediated effector functions or antibody dependent cytotoxicity are largely unknown. Furthermore, the role of the innate immune system for the control of infection by antibodies remains largely unknown. An understanding of the molecular mechanisms underlying antibody-mediated control during the acute phase of infection in subjects that naturally clear their infections and in subjects that eventually have chronic infections will provide information on correlates of immune protection and inform about vaccine design. Our central hypothesis is that both, innate and adaptive immune responses are required for spontaneous clearance of HCV infection. We hypothesize that Fc-mediated effector functions are one of the main determinants for viral clearance and that other innate factors further contribute to the antiviral response. Understanding the functional differences in the quality of the antibody response in patients with acute self-limited and chronic infections will provide crucial information for rational design of urgently needed vaccines for protection against chronic HCV infection.

• DFG Programme: Research Fellowships
• International Connection: France
• Host: Professor Dr. Thomas Baumert