Described herein is a method of eliciting antibodies and neutralizing ofbinding antibodies against a hepatitis C virus (HCV) E1E2 or E2 antigen usingHCV 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 responsesand/or anti-E2 NOB antibody responses to HCV and to provide prophylactic ortherapeutic treatment against HCV infection.