An affinity improved single-chain antibody from phage display of a library derived from monoclonal antibodies detects fumonisins by immunoassay

Anal Chim Acta. 2015 Mar 31:867:74-82. doi: 10.1016/j.aca.2015.02.014. Epub 2015 Feb 10.

Abstract

Fumonisin B analogs, particularly FB1, FB2, and FB3, are major mycotoxins found in cereals. Single-chain fragment variable (scFv) antibodies represent a promising alternative immunoassay system. A phage-displayed antibody library derived from four monoclonal antibodies (mAbs) generated against FB1 was used to screen high binding affinity scFv antibodies; the best candidate was designated H2. Surface plasmon resonance measurements confirmed that the H2 scFv displayed a 82-fold higher binding affinity than its parent mAb. Direct competitive enzyme-linked immunosorbent assay demonstrated that the H2 antibody could competitively bind to free FB1, FB2, and FB3, with an IC50 of 0.11, 0.04, and 0.10 μM, respectively; it had no cross-reactivity to deoxynivalenol, nivalenol and aflatoxin. Validation assays with naturally contaminated samples revealed a linear relationship between the H2 antibody-based assay results and chemical analysis results, that could be expressed as y=1.7072x+5.5606 (R(2)=0.8883). Homology modeling of H2 revealed a favorable binding structure highly complementary to the three fumonisins. Molecular docking analyses suggested that the preferential binding of the H2 scFv to FB2 was due to the presence of a hydrogen radical in its R1 position, leading to a proper electrostatic matching and hydrophobic interaction. The H2 scFv antibody can be used for the rapid, accurate, and specific detection of fumonisin contamination in agricultural samples.

Keywords: Binding kinetics; Direct competitive enzyme-linked immunosorbent assay; Fumonisin; Monoclonal recombinant antibody; Phage display.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody Affinity*
  • Cell Line
  • Cross Reactions
  • Fumonisins / analysis*
  • Fumonisins / immunology
  • Hybridomas / cytology
  • Immunoassay*
  • Kinetics
  • Molecular Docking Simulation
  • Peptide Library*
  • Protein Conformation
  • Sequence Analysis
  • Single-Chain Antibodies / chemistry
  • Single-Chain Antibodies / immunology*
  • Solubility

Substances

  • Fumonisins
  • Peptide Library
  • Single-Chain Antibodies