Ecobody technology: rapid monoclonal antibody screening method from single B cells using cell-free protein synthesis for antigen-binding fragment formation

Sci Rep. 2017 Oct 25;7(1):13979. doi: 10.1038/s41598-017-14277-0.

Abstract

We report a rapid and cost-effective monoclonal antibody screening method from single animal B cells using reverse transcription (RT)-PCR and Escherichia coli cell-free protein synthesis (CFPS), which allows evaluation of antibodies within 2 working days. This process is named "Ecobody technology". The method includes strategies to isolate B cells that specifically bind an antigen from the peripheral blood of immunised animals, and single-cell RT-PCR to generate DNA fragments of the VH and VL genes, followed by CFPS for production of fragments of antigen binding (Fab). In the CFPS step, we employed our techniques: 1) 'Zipbody' as a method for producing Fab, in which the association of heavy and light chains is facilitated by adhesive leucine zipper peptides fused at the C-termini of the Fab; and 2) an N-terminal SKIK peptide tag that can increase protein expression levels. Using Ecobody technology, we obtained highly-specific monoclonal antibodies for the antigens Vibrio parahaemolyticus and E. coli O26. The anti-V. parahaemolyticus Zipbody mAb was further produced in E. coli strain SHuffle T7 Express in inclusion bodies and refolded by a conventional method, resulting in significant antigen-binding activity (K D = 469 pM) and productivity of 8.5 mg purified antibody/L-culture.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / isolation & purification
  • Antibodies, Monoclonal / metabolism*
  • Antigens, Bacterial / immunology
  • Antigens, Bacterial / metabolism*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • Cell-Free System
  • Enzyme-Linked Immunosorbent Assay
  • Escherichia coli / immunology
  • Escherichia coli / metabolism
  • Immunoglobulin Fab Fragments / immunology
  • Immunoglobulin Fab Fragments / metabolism*
  • Immunoglobulin Heavy Chains / immunology
  • Immunoglobulin Heavy Chains / metabolism*
  • Immunoglobulin Light Chains / immunology
  • Immunoglobulin Light Chains / metabolism*
  • Protein Biosynthesis*
  • Protein Engineering / methods*
  • Rabbits
  • Vibrio parahaemolyticus / immunology
  • Vibrio parahaemolyticus / metabolism

Substances

  • Antibodies, Monoclonal
  • Antigens, Bacterial
  • Immunoglobulin Fab Fragments
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains