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 antibodies (mAbs) against the surface antigens of HBV would offer several advantages over the current human polyclonal antibody. We have developed a humanized antibody with specificity for the preS2 surface antigen of HBV and evaluated the neutralizing activity of the humanized antibody. The complementarity-determining regions of the heavy and light chains of a murine monoclonal antibody (H8) were grafted onto the variable regions of a highly homologous human anti-Sm antibody, which were then combined with the constant regions of human gamma 1 and kappa, respectively. The affinity of the resulting humanized antibody (Z6B) was 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 chimeric antibody. The evaluation of the HBV neutralizing activity of ZP39 using in vitro infection of adult human hepatocyte primary culture by HBV showed that it had a specific activity that was approximately 1000 times 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.
Park
S S
SS
Antibody Engineering Research Unit, Korea Research Institute of Bioscience and Biotechnology, Taejon, Korea.
Ryu
C J
CJ
Gripon
P
P
Guguen-Guillouzo
C
C
Hong
H J
HJ
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology*; D001483:Base Sequence; D006509:Hepatitis B / Q000517:prevention & control; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; C050807:presurface protein 2, hepatitis B surface antigen