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HC-1, an IgG2 HCV-neutralizing domain B hmAb, recognizes a conformational epitope on HCV E2 and at a critical antibody concentration is able to completely suppress viral replication. In addition, this antibody binds broadly with known contact residues that are absolutely conserved. However, the neutralization potency is modest to moderate against some isolates, which limits its therapeutic applications. Through improve HC-1 antibody binding and neutralization by affinity maturation. In vitro antibody displays, both phage and yeast, have been widely employed to increase antibody affinity. The advantages of yeast over phage display include avoiding expression, purification, and characterization of a large number of different phage display scFv, the ability to measure KD directly on the yeast surface, and the ability to enrich for higher affinity clones with decreasing antigen concentration by flow cytometry.