Described herein is a method of eliciting antibodies and neutralizing of binding antibodies against a hepatitis C virus (HCV) E1E2 or E2 antigen using HCV E2 or HCV E1E2 polypeptides and/or HCV E2 or E1E2 polynucleotides. Elicitation of anti-E2 antibodies and anti-E2 NOB antibodies can be used, inter alia, to provide model systems to optimize anti-E2 antibody responses and/or anti-E2 NOB antibody responses to HCV and to provide prophylactic or therapeutic treatment against HCV infection.