Determination of the human antibody response to the neutralization epitopes encompassing amino acids 313-327 and 432-443 of hepatitis C virus E1E2 glycoproteins

It has been reported that monoclonal antibodies (MAbs) to the E1E2 glycoproteins may have the potential to prevent hepatitis C virus (HCV) infection. The protective epitopes targeted by these MAbs have been mapped to the regions encompassing amino acids 313-327 and 432-443. In this study, we synthesized these two peptides and tested the reactivity of serum samples from 336 patients, 210 of which were from Chronic Hepatitis C (CHC) patients infected with diverse HCV genotypes. The remaining 126 samples were isolated from patients who had spontaneously cleared HCV infection. In the chronic HCV-infected group (CHC group), the prevalence of human serum antibodies reactive to epitopes 313-327 and 432-443 was 24.29% (51 of 210) and 4.76% (10 of 210), respectively. In the spontaneous clearance group (SC group), the prevalence was 0.79% (1 of 126) and 12.70% (16 of 126), respectively. The positive serum samples that contained antibodies reactive to epitope 313-327 neutralized HCV pseudoparticles (HCVpp) bearing the envelope glycoproteins of genotypes 1a or 1b and/or 4, but genotypes 2a, 3a, 5 and 6 were not neutralized. The neutralizing activity of these serum samples could not be inhibited by peptide 313-327. Six samples (SC17, SC38, SC86, SC92, CHC75 and CHC198) containing antibodies reactive to epitope 432-443 had cross-genotype neutralizing activities. The neutralizing activity of SC38, SC86, SC92 and CHC75 was partially inhibited by peptide 432-443. However, the neutralizing activity of sample SC17 for genotype 4HCVpp and sample CHC198 for genotype 1b HCVpp were not inhibited by the peptide. This study identifies the neutralizing ability of endogenous anti-HCV antibodies and warrants the exploration of antibodies reactive to epitope 432-443 as sources for future antibody therapies.