Chimeric monoclonal antibodies to hypervariable region 1 of hepatitis C virus

Abstract

Two chimeric monoclonal antibodies (cAbs), 2P24 and 15H4, to hypervariable region 1 (HVR1) of hepatitis C virus (HCV) were constructed by grafting the variable regions of murine monoclonal antibodies (mAbs) 2P24 and 15H4 to a human IgG1 kappa constant region. Two cAb-producing cell lines were adapted to serum-free media. Both cAb 2P24 and cAb 15H4 cell lines produced 3-5 microg antibodies ml(-1) after 3-5 days culture. cAbs retained binding characteristics similar to those observed in the original mAbs. There was no clear difference in affinity between binding of cAbs and mAbs to seven HVR1 peptides. Mixtures of biotinylated cAbs or mAbs reacted with 32 (86 %) and 31 (84 %) of 37 HVR1 peptides, respectively, but not with non-HVR1 control peptides. HCV from 16 out of 18 (89 %) random HCV-containing plasmas was captured by the mixture of biotinylated cAbs. The capture from IgG-depleted plasmas suggested that cAbs captured mainly free rather than complexed HCV, irrespective of genotype. A mixture of the two cAbs inhibited HCV binding to Molt-4 cells in a dose-dependent manner. These cAbs may be useful for prevention of nosocomial HCV infection and passive immunization to prevent HCV reinfection after liver transplantation.