GENERATION AND CHARACTERIZATION OF A HUMANIZED ANTIBODY WITH SPECIFICITY FOR PRES2 SURFACE-ANTIGEN OF HEPATITIS-B VIRUS

For the prevention of hepatitis B virus (HBV) infection, monoclonal an tibodies (mAbs) against the surface antigens of HBV would offer severa l advantages over the current human polyclonal antibody. We have devel oped a humanized antibody with specificity for the preS2 surface antig en of HBV and evaluated the neutralizing activity of the humanized ant ibody, The complementarity-determining regions of the heavy and light chains of a murine monoclonal antibody (H8) were grafted onto the vari able regions of a highly homologous human anti-Sm antibody, which were then combined with the constant regions of human gamma 1 and kappa, r espectively. The affinity of the resulting humanized antibody (Z6B) wa s about one tenth that of the chimeric antibody, The new version (ZP39 ) of the humanized antibody, which was constructed by substituting the heavy-chain framework residue at position 94 of the Z6B with original mouse residue, showed almost the same affinity as that of the chimeri c antibody, The evaluation of the HBV neutralizing activity of ZP39 us ing in vitro infection of adult human hepatocyte primary culture by HB V showed that it had a specific activity that was approximately 1000 t imes higher than commercially available polyclonal hepatitis B immune globulin, We expect that the present humanized antibody will be useful in the prevention of HBV infection.