Identification and Characterization of Immunodominant Epitopes on Hepatitis C Viral Envelope Protein Associated with Infection Outcome
2The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Israel
Hepatitis C virus (HCV) is a leading cause of liver disease. Approximately 25% of infected patients clear the virus spontaneously. It is widely accepted that antibodies present in these clearers have a wide neutralization breadth. Although there is a significant progress in HCV treatment, there is still a need for developing effective anti-HCV vaccines. We therefore investigated immunodominant epitopes on the HCV-E2 envelope protein contributing to successful antibody-mediated neutralization.
We undertook an unbiased approach by screening a random phage-display library presenting various peptides to detect binders to antibodies in sera obtained from spontaneous-clearers (SC) and chronically-infected (CI) patients. By repetitive rounds of biopanning followed by sequencing of the binding peptides, we identified enriched peptide-sequences that were aligned to HCV-E2. The most significantly enriched epitopes were synthesized as peptides and tested in binding and neutralization assays. To evaluate the potential of these epitopes to induce broad neutralizing antibody response, ICR-mice were immunized with the different peptides.
We identified epitopes that are abundant more in CIs or in SCs. Among these we identified the well-known immunodominant epitopes on HCV-E2. We found that epitope I (a neutralizing epitope) is unique to SCs and contributes to efficient HCV-neutralization, while epitope II (an interfering epitope) is unique to CIs. Furthermore, mice vaccinated with peptides unique to SCs showed higher potency and breadth of viral neutralization.
This study identifies neutralization epitopes that are associated with viral clearance and induce a broader antibody immune response and is expected to lead to rational design of anti-HCV peptide-based vaccine.