The original IgG2 HC-1 antibody was isolated from peripheral blood B cells of an individual with chronic HCV genotype 1a infection who had a high serum antibody binding titer to E2 and high neutralizing activity (>1:10,000 titer) against genotype 1a HCVpp. The B cells were activated by Epstein-Barr virus and used to produce human hybridomas. The affinity-matured version of HC-1 (called HC-1AM) was created by constructing a library of yeast-displayed HC-1 single chain Fv (scFv) mutants and selecting the relevant high affinity binders.