Generation and characterization of a novel tetravalent bispecific antibody that binds to hepatitis B virus surface antigens

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Title
Generation and characterization of a novel tetravalent bispecific antibody that binds to hepatitis B virus surface antigens
Author(s)
Sung Sup Park; Chun Jeih Ryu; Young Jun Kang; S V S Kashimiri; Hyo Jeong Hong
Bibliographic Citation
Molecular Immunology, vol. 37, no. 18, pp. 1123-1130
Publication Year
2000
Abstract
Hepatitis B virus (HBV) infection is a worldwide public health problem affecting about 350 million people. HBV envelope contains three surface antigens, called pre-S1, pre-S2 and S. For the prophylaxis of HBV infection, only an anti-S monoclonal antibody was tested for the protective efficacy against HBV infection, but it was shown to be incomplete. In addition, some immune escape mutants carrying mutations on the S antigen were reported. Therefore, a multivalent bispecific antibody rather than a single monoclonal antibody would be more beneficial for the prophylaxis of HBV infection. We have generated a novel tetravalent bispecific antibody with two binding sites for each of the S and pre-S2 antigens. Each of the antigen-binding sites was composed of a single-chain Fv (ScFv). The tetravalent antibody was generated by constructing a single gene encoding a single-chain protein. This protein consisted of an anti-S ScFv whose carboxyl end was tethered, through a 45 amino acid linker, to the amino terminus of anti-preS2 ScFv that in turn was joined to the hinge region of human γ1 constant region. The single-chain protein was expressed in Chinese hamster ovary cells and secreted in culture supernatant as a homodimeric molecule. The tetravalent bispecific antibody showed both anti-S and anti-pre-S2 binding activities. In addition, the binding affinity of the bispecific antiboy for HBV particles was greater than that of either parental antibody. The tetravalent bispecific antibody is a potentially useful reagent for the prevention and treatment of HBV infection.
Keyword
antibody engineeringbispecific antibodyhepatitis B virussingle-chain antibody
ISSN
0161-5890
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/S0161-5890(01)00027-X
Type
Article
Appears in Collections:
Aging Convergence Research Center > 1. Journal Articles
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