Antigenicity and immunogenicity of the hepatitis C virus envelope E2 protein

The absence of an available animal model or a consistent in vitro culture system for the replication of the hepatitis C virus (HCV), have seriously limited the research on the immunological role of their main antigens. In the present paper, four HCV E2 protein variants were obtained from recombinant microorganisms. Particularly, the E2.680 protein (384-680 aa) constitutes the first E2 protein variant obtained from recombinant Picchia pastoris. Moreover, peptides covering different regions of the HCV E2 protein were synthesized. The recombinant proteins and synthetic peptides were used to study the recognition of HCV infected human sera. As a result, we describe for the first time the existence of an immunologically relevant region covering not only the HVR-I but also the region up to 473 aa in the HCV polyprotein. Furthermore, it was demonstrated that the E2.680 protein was recognized by a specific monoclonal antibody for conformational epitopes. This is the first evidence of an E2 variant obtained from recombinant microorganisms containing regions that are conformationally similar to the viral antigen. The recombinant protein variants and the synthetic peptide of the HVR-I, were able to induce high titers of specific antibodies in animal models, but the E2.680 variant additionally induces a specific cellular immune response. We conclude that, the Nterminal region of the HCV E2 protein plays a main role in antigenicity and viral immunogenicity. Therefore, the E2.680 protein and the HVR-I synthetic peptide obtained are available analytical tools and can potentially become components of a vaccine candidate against HCV.