The way to the peptide vaccine against hepatitis C

Abstract

In order to overcome the problem of genetic variability of hepatitis C virus (HCV) envelope proteins during vaccine development, we have used the so-called “reverse vaccinology” approach defined as “from genome to vaccine.” In the context of this approach we have created a database of amino acid sequences of HCV proteins, performed an analysis of the viral genome, and identified several highly conserved regions in HCV envelope proteins. These regions demonstrated low antigenic activity within full-length proteins and viral particles: antibodies against these regions were found not in all hepatitis C patients. However, among highly conserved regions, two regions, containing a wide set of potential T-helper epitope motifs were identified. Using solid-phase peptide synthesis we have generated several synthetic peptide constructs, which consist of two highly conservative sites of the HCV envelope protein E2 joint by a linker; one of these sites contained a set of T-helper epitope motifs. In experiments on laboratory animals the resultant peptide constructs exhibited immunogenicity comparable to the immunogenicity of the protein molecules and were able to induce generation of antibodies, which specifically bound HCV envelope proteins. Immunization with certain constructs resulted in generation of antibodies that were able to bind HCV from the blood plasma of hepatitis C patients. Based on these peptide constructs an original preparation of the synthetic peptide vaccine against hepatitis C is now under development.