Identification of HBsAg-specific antibodies from a mammalian cell displayed full-length human antibody library of healthy immunized donor

Cell Mol Immunol. 2012 Mar;9(2):184-90. doi: 10.1038/cmi.2011.55. Epub 2011 Dec 19.

Abstract

Hepatitis B immunoglobulin (HBIG) is important in the management of hepatitis B virus (HBV) infection. Aiming to develop recombinant monoclonal antibodies as an alternative to HBIG, we report the successful identification of HBV surface antigen (HBsAg)-specific antibodies from a full-length human antibody library displayed on mammalian cell surface. Using total RNA of peripheral blood mononuclear cells of a natively immunized donor as template, the antibody repertoire was amplified. Combining four-way ligation and the Flp recombinase-mediated integration (Flp-In) system, we constructed a mammalian cell-based, fully human, full-length antibody display library in which each cell displayed only one kind of antibody molecule. By screening the cell library using fluorescence-activated cell sorting (FACS), eight cell clones that displayed HBsAg-specific antibodies on cell surfaces were identified. DNA sequence analysis of the antibody genes revealed three unique antibodies. FACS data indicated that fluorescent strength of expression (FSE), fluorescent strength of binding (FSB) and relative binding ability (RBA) were all different among them. These results demonstrated that by using our antibody mammalian display and screening platform, we can successfully identify antigen-specific antibodies from an immunized full-length antibody library. Therefore, this platform is very useful for the development of therapeutic antibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Affinity
  • CHO Cells
  • Cloning, Molecular
  • Cricetinae
  • Epitopes / immunology
  • Gene Library*
  • Hepatitis B / immunology*
  • Hepatitis B / prevention & control
  • Hepatitis B / transmission
  • Hepatitis B Antibodies / genetics
  • Hepatitis B Antibodies / immunology*
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology*
  • Humans
  • Protein Binding
  • Viral Hepatitis Vaccines / genetics
  • Viral Hepatitis Vaccines / immunology*

Substances

  • Epitopes
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Viral Hepatitis Vaccines