Antibodies against hepatitis C virus-like particles and viral clearance inacute and chronic hepatitis C

We recently described the efficient assembly of hepatitis C virus (HCV) str uctural proteins into HCV-like particles (HCV-LPs) in insect cells. These n oninfectious HCV-LPs have similar morphologic and biophysical properties as putative virions isolated from HCV-infected humans and can induce a broadl y directed immune response in animal models. The HCV envelope proteins of H CV-LPs are presumably presented in a native, virion-like conformation and m ay therefore interact with antienvelope antibodies directed against conform ational epitopes, In this study, HCV-LPs were used as capture antigens in a n enzyme-linked immunosorbent assay (ELISA) to detect and quantify antibodi es against HCV structural proteins in patients with acute and chronic hepat itis C, High titers of anti-HCV-LP antibodies were detected in patients chr onically infected with HCV genotypes 1 to 6. In contrast to individuals wit h chronic hepatitis C, patients with acute self-limited hepatitis C display ed only a transient and weak seroreactivity against HCV-LPs. Patients with chronic HCV infection successfully treated with interferon demonstrated a g radual decline of anti-HCV-LP titers during or subsequent to viral clearanc e. Sustained interferon responders were characterized by significantly high er pretreatment levels of anti-HCV-LP antibodies as compared with nonrespon ders (P = .0001). In conclusion, HCV infection is associated with limited h umoral immunity against the envelope proteins present on the HCV-LPs. An HC V-LP-based ELISA may be a useful diagnostic tool to distinguish acute hepat itis C from chronic HCV infection with exacerbation, and to predict viral c learance in response to interferon.