Neutralizing antibodies in patients with chronic hepatitis C infection treated with (Peg)-interferon/ribavirin.

BACKGROUND: The role of neutralizing antibody (NAb) in determining response to antiviral therapy has not been established. OBJECTIVE: In this study we have analysed the kinetic's of the NAb response in patients with chronic hepatitis C who received antiviral therapy. STUDY DESIGN: Seventeen patients infected with genotype 1, 2a/c or 3a hepatitis C virus (HCV) were enrolled, eight with a sustained virological response (SVR), five non-responders and four relapsers. RESULTS: The mean NAb titre required to neutralize 50% of the E1E2-pp in patients who achieved an SVR (294+/-S.D. 51), in relapsers (246+/-S.D. 61.7) and non-responders (286+/-S.D. 80.95) did not differ significantly between the patient groups and did not alter during the course of treatment (P>0.01). Genetic variation present before antiviral therapy was analysed by single strand conformation polymorphism (SSCP) and failed to demonstrate a significant difference in the mean number of amplified E1E2 DNA fragments from the serum of patients who achieved an SVR (3.15+/-S.D. 1.53), relapsers (2.8+/-S.D. 1.32) or non-responders (3.69+/-S.D. 1.75). The baseline serum HCV viral loads were also not significantly different between patients who achieved an SVR (1.4 x 10(6) copies/ml; +/-S.D. 2.4 x 10(6)), relapsers (1.3 x 10(7) copies/ml; +/-S.D. 2.4 x 10(7)) and non-responders (1.5 x 10(6) copies/ml; +/-S.D. 1.1 x 10(6)). CONCLUSION: We have shown that neutralizing anti-HCVpp antibody is not associated with response to antiviral therapy. In addition, there was no correlation between baseline virological load, circulating viral quasi-species, NAb titres and final response to treatment.

A self-adjuvanting multiepitope immunogen that induces a broadly cross-reactive antibody to hepatitis C virus.

UNLABELLED: We describe a peptide-based strategy for HCV vaccine design that addresses the problem of variability in hypervariable region 1 (HVR1). Peptides representing antibody epitopes of HVR1 from genotype 1a were synthesized and incorporated into multideterminant immunogens that also included lipid moieties and helper T (T(h)) cell epitopes. Mice inoculated with these polyepitopes generated strong antibody responses. Antibody titers were highest in mice inoculated with polyepitope immunogens which contained the lipid moiety dipalmitoyl-S-glyceryl cysteine (Pam2Cys). Antisera were tested for their potential to neutralize HCV by 3 currently available assays. Antibodies elicited in mice by the polyepitope-based vaccine candidates were able to (1) bind to E2 expressed on the surface of E1/E2-transfected human embryonic kidney (HEK) 293T cells, (2) capture HCV of different genotypes (1, 2, and 3) from the serum of chronically infected humans in an immune capture RT-PCR assay and (3) inhibit HCVpp entry into Huh7 cells. Antibody present in the sera of patients chronically infected with HCV genotypes 1, 2, 3, and 4 also bound to the HVR1-based polyepitope. CONCLUSION: These results demonstrate the potential of self-adjuvanting epitope-based constructs in the development and delivery of cross-reactive immunogens that incorporate potential neutralizing epitopes present within the viral envelope of HCV.