Available for licensing and commercial development are compositions and methods for preventing and/or treating infection caused by hepatitis C virus (HCV). The invention is based on mapping studies conducted by the inventors of two epitopes within HCV E2: epitope I and epitope II. It has been discovered that epitope I is involved in virus neutralization but that epitope II mediates antibody interference, probably an adaptation of the virus to obfuscate the immune system. In an effort to attenuate or disable the interference effect of HCV-E2 epitope II, the present invention is directed to a HCV E2 polypeptide substitution/deletion of native amino acids LFY in epitope II, a HCV E2 polypeptide insertion of amino acids between the native LFY in epitope II, or the use of epitope II as a molecular decoyant or to affinity-purify an immune globulin to deplete interfering antibodies from, and enrich neutralizing antibodies in, the preparation.