Expression, purification and in vitro refolding of the recombinant truncated Saposin-like protein 2 antigen for development of diagnosis of human fascioliasis

Acta Trop. 2017 Jul:171:163-171. doi: 10.1016/j.actatropica.2017.03.002. Epub 2017 Mar 11.

Abstract

Early diagnosis of fascioliasis is critical in prevention of injury to the liver and bile ducts. Saposin-like protein (FhSAP-2) is probably the most ideal antigen of Fasciola hepatica for development of ELISA kits. SAP-2 has a conserved tertiary structure containing three disulfide bonds and conformational epitopes. Therefore, antigenicity of SAP-2 is greatly depends on disulfide bond formation and proper folding. We produced the recombinant truncated SAP-2 (rtSAP-2) in the SHuffle® T7 and Rosetta strain of Escherichia coli, in soluble and insoluble forms, respectively and purified by immobilized metal affinity chromatography (IMAC). The refolding process of denatured rtSAP-2 was performed using dialysis and dilution methods in the presence of chemical additives, along with reduced/oxidized glutathione (in vitro). Physicochemical studies, including non-reducing gel electrophoresis, Ellman's assay, Western blotting and ELISA showed the most antigenicity and likely correct folding of rtSAP-2, which was obtained by dialysis method. An IgG ELISA test was developed using rtSAP-2 refolded by dialysis and compared with excretory/secretory products of parasite with 52 positive fascioliasis samples, 79 other parasitic samples and 70 negative controls samples. The results exhibited 100% sensitivity and 98% specificity for rtSAP-2, also, 100% and 95.3% for excretory/secretory (E/S) antigen, respectively. In conclusion, it is suggested that rtSAP-2 with the correct folding could be used as a candidate antigen for detection of human fascioliasis.

Keywords: Antigenicity; ELISA; Fasciola hepatica; In vitro refolding; rtSAP-2.

MeSH terms

  • Animals
  • Antibodies, Helminth / immunology
  • Antigens, Helminth / chemistry
  • Antigens, Helminth / immunology
  • Antigens, Helminth / metabolism*
  • Chromatography, Affinity
  • Enzyme-Linked Immunosorbent Assay / methods*
  • Fasciola hepatica / immunology*
  • Fascioliasis / diagnosis*
  • Fascioliasis / parasitology
  • Helminth Proteins / immunology*
  • Humans
  • Protein Folding
  • Saposins / immunology*
  • Sensitivity and Specificity
  • Serologic Tests

Substances

  • Antibodies, Helminth
  • Antigens, Helminth
  • Helminth Proteins
  • Saposins