A humanized antibody with specificity for hepatitis B surface antigen.
A murine monoclonal antibody H67 was characterized for the binding specificity, which showed that H67 recognizes a disulfide-bond-dependent conformational epitope of common a antigenic determinant on the hepatitis B surface antigen. The result suggested that this antibody may have the potential of replacing hepatitis B immune globulin in the prevention of hepatitis B virus (HBV) infection. Therefore, we have constructed the humanized antibody HuS10 by grafting the complementarity determining regions and some framework amino acid residues of H67 onto the most homologous human antibody variable regions, 21/28 for heavy chain variable region and B1 and J kappa 2 for light chain variable region, followed by combining with human constant regions C gamma 1 and C kappa. The affinity of the HuS10 was the same as that of the H67, 8 x 10(8) x 10(8)M-1, and the HuS10 neutralized the in vitro infection of adult human hepatocyte primary culture by adr or ayw subtype of HBV. The neutralization assay showed that the HuS10 had approximately 2,000-times higher specific activity than commercially available polyclonal HBIG. These results suggest that the humanized antibody will be useful in the prevention or treatment of HBV infection.
Ryu
C J
CJ
Antibody Engineering Research Unit, Korea Research Institute of Bioscience and Biotechnology, KIST, Yuseong, Taejeon, Korea.
Padlan
E A
EA
Jin
B R
BR
Yoo
O J
OJ
Hong
H J
HJ
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000918:Antibody Specificity; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D004797:Enzyme-Linked Immunosorbent Assay; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006801:Humans; D006825:Hybridomas; D007135:Immunoglobulin Variable Region / Q000276:immunology; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D017386:Sequence Homology, Amino Acid
D000911:Antibodies, Monoclonal; D006514:Hepatitis B Surface Antigens; D007135:Immunoglobulin Variable Region