A composition comprising a hepatitis C virus (HCV) Envelope 2 (E2) polypeptide including a receptor binding variant, wherein the polypeptide is modified to comprise: (i) a cysteine mutated or disrupted at 2, 3, or 4 cysteines selected from C452, C486, C569, and C597 and wherein the polypeptide forms substantially fewer multimers by intermolecular disulfide bonding relative to the HCV E2 polypeptide without cysteine modification, and substantially retains CD81 binding and various uses thereof. A method of producing a composition comprising at least 40%, or at least 45%, or at least 50%, or at least 55%, or at least 60%, or at least 65%, or at least 70% monomelic HCV E2 polypeptide, the method comprising expressing a polypeptide in a host cell and isolating the expressed product, wherein the polypeptide is an HCV E2 polypeptide including a receptor binding variant, and wherein the polypeptide is modified to comprise: (i) a cysteine mutated or disrupted at 2, 3, or 4 cysteines selected from C452, C486, C569, and C597.
