1. ¹Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia
2. ²Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, Australia
3. ³The Burnet Institute, Alfred Medical Research and Education Precinct, Prahran, Victoria, Australia

Correspondence: Dr DC Jackson, Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria 3010, Australia. E-mail: davidcj@unimelb.edu.au; Dr J Torresi, Department of Medicine (RMH/WH), The University of Melbourne, Post Office, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia. E-mail: josepht@unimelb.edu.au

Received 13 July 2006; Accepted 17 August 2006; Published online 23 January 2007.

Abstract

We describe a peptide-based strategy for hepatitis C virus (HCV) vaccine design that exploits synthetic peptides representing antibody epitopes of the hypervariable region 1 (HVR1) of the E2 glycoprotein and also less variable regions immediately downstream of HVR1. These epitopes were linked to a T-helper (T_h) epitope (KLIPNASLIENCTKAEL) derived from the Morbillivirus canine distemper virus. Antibody titres induced by the two vaccine candidates T_h-A (E2 amino acid 384–414) and T_h-B (E2 amino acid 390–414) were significantly higher than those produced against vaccines lacking the T_h epitope (P<0.05). Mice inoculated with the vaccine candidates T_h-C (E2 amino acids 412–423) and T_h-F (E2 amino acids 436–447) emulsified in complete Freund's adjuvant each elicited antibody titres that were significantly higher than those elicited by T_h-E (E2 amino acids 396–407) and T_h-D (E2 amino acids 432–443) (P<0.01). Antisera obtained from mice inoculated with the epitope vaccines T_h-A, T_h-B, T_h-D and T_h-E bound to E2 expressed at the surface of 293T cells that had been transfected with E1E2. Furthermore, IgG from the sera of mice inoculated with four of the vaccine candidates, T_h-A, T_h-C, T_h-D and T_h-E, inhibited the entry of HCV/human immunodeficieny virus pseudoparticles (HCVpps) into Huh-7 cells. These results demonstrate the potential of synthetic peptide-based constructs in the delivery of potential neutralizing epitopes that are present within the viral envelope of HCV.