Bedeutung der Hepatitis C Virus Genprodukte E1 und E2/NS1 fuer die Virusneutralisation Schlussbericht

Chronic infection develops in more than 50% of HCV infected patients. The molecular mechanism involved in the high rate of viral persistence is not understood. We investigated the role of antibodies directed to the putative HCV envelope proteins E1 and E2 for the neutralization of virus. An in vitro neutralization assay was established with human fibroblasts for the characterization of such antibodies. Different regions of the envelope were used for immunization. The presence of antibodies in sera of patients was investigated by Western-blot, immunoprecipitation and pep-scan analysis. Different time points, as well as different courses of infection were systematically studied by a retrospective analysis of patients who were infected with the same isolate (HCV-AD78). Antibodies directed against different regions of the envelope were studied in the in vitro neutralization assay. We found that antibodies in sera of patients and in hyperimune sera could neutralize HCV-AD78 in vitro. Such antibodies were directed against hypervariable region 1 (HVR1) or against other, unknown epitopes within envelope protein E2. The early development of antibodies (up to 12 months p.i.) was found to correlate with resolving from disease. The method of DNA vaccination of mice was found to result in high titres of HCV envelope-specific antibodies. The complete genome of HCV-AD78 was cloned and sequenced. The results of this project are important for the development of a future HCV vacinne. (orig.)SIGLEAvailable from TIB Hannover: DtF QN1(58,23) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman