Project Details
Projekt
Modeling of the transfer of adoptive immunity to hepatitis B and C virus in liver transplantation
Applicant
Dr. Melanie Fiedler
Subject Area
General and Visceral Surgery
Term
from 2008 to 2011
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 5397027
During the first funding period, our group has demonstrated the principal possibility of a transfer of cellular and humoral HBV-specific immunity by liver transplantation after immunization of donors with a highly immunogenic HBV vaccine. In the current study, this investigation will be extended by inclusion of a larger number of patients. A more difficult situation is observed in the research activities directed at the prevention of HCV reinfection of liver-transplanted patients. The resolution of HCV infection was found to be strongly associated with vigorous cell mediated immune responses to NS3 and NS5. Virus-neutralizing antibodies might also play a role in the clearance of HCV. The primary aim of this project is the development of a prototype HCV vaccine, which in perspective may be used for immunization of donors in order to prevent reinfection of the transplanted liver with HCV. To this end, we intend to use virus-like particles (VLPs) based on HBV nucleocapsid as a carrier of the fragments of HCV proteins NS3, NS5, and E2, bearing Th and B-cell epitopes. These chimeric recombinant VLPs should induce HCV-specific cellular and humoral immune responses. The prepared VLPs will be used for immunization in mice. The best chimeric VLPs will subsequently be used in experiments on transfer of adoptive immunity to HCV by liver transplantation in rats. These preclinical model experiments will evaluate the principal feasibility of the adoptive transfer scheme for HCV by liver transplantation.
DFG Programme
Clinical Research Units
Participating Persons
Professorin Dr. Monika Lindemann; Professor Dr. Sergei Viazov
