Production and characterization of antibody against Opisthorchis viverrini via phage display and molecular simulation

PLoS One. 2021 Mar 23;16(3):e0248887. doi: 10.1371/journal.pone.0248887. eCollection 2021.

Abstract

In this study, a key issue to be addressed is the safe disposal of hybridoma instability. Hybridoma technology was used to produce anti-O. viverrini monoclonal antibody. Previous studies have shown that antibody production via antibody phage display can sustain the hybridoma technique. This paper presents the utility of antibody phage display technology for producing the phage displayed KKU505 Fab fragment and using experiments in concomitant with molecular simulation for characterization. The phage displayed KKU505 Fab fragment and characterization were successfully carried out. The KKU505 hybridoma cell line producing anti-O. viverrini antibody predicted to bind to myosin was used to synthesize cDNA so as to amplify the heavy chain and the light chain sequences. The KKU505 displayed phage was constructed and characterized by a molecular modeling in which the KKU505 Fab fragment and -O. viverrini myosin head were docked computationally and it is assumed that the Fab fragment was specific to -O. viverrini on the basis of mass spectrometry and Western blot. This complex interaction was confirmed by molecular simulation. Furthermore, the KKU505 displayed phage was validated using indirect enzyme-linked immunosorbent assays (ELISA) and immunohistochemistry. It is worthy to note that ELISA and immunohistochemistry results confirmed that the Fab fragment was specific to the -O. viverrini antigen. Results indicated that the approach presented herein can generate anti-O. viverrini antibody via the phage display technology. This study integrates the use of phage display technology together with molecular simulation for further development of monoclonal antibody production. Furthermore, the presented work has profound implications for antibody production, particularly by solving the problem of hybridoma stability issues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Helminth / biosynthesis*
  • Antibodies, Helminth / chemistry
  • Antibodies, Helminth / immunology*
  • Antigens, Helminth / chemistry
  • Antigens, Helminth / immunology
  • Biliary Tract / immunology
  • Biliary Tract / parasitology
  • Cattle
  • Immunoglobulin Fab Fragments / chemistry
  • Immunoglobulin Fab Fragments / immunology
  • Mice
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation*
  • Myosins / chemistry
  • Opisthorchis / immunology*
  • Peptide Library*
  • Reproducibility of Results
  • Serum Albumin, Bovine / analysis

Substances

  • Antibodies, Helminth
  • Antigens, Helminth
  • Immunoglobulin Fab Fragments
  • Peptide Library
  • Serum Albumin, Bovine
  • Myosins

Grants and funding

This research has been funded by the MSc scholarship from the centre for research and development of medical diagnostic laboratories, Liver fluke and cholangiocarcinoma research center, and the Graduate School, Khon Kaen University, Thailand. CN is grateful for financial support by the Center of Excellence on Medical Biotechnology (CEMB), the S&T Postgraduate Education and Research Development Office (PERDO) and the Office of Higher Education Commission (OHEC), Thailand. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.