Generation and molecular characterization of a monoclonal antibody reactive with conserved epitope in sphingomyelinases D from Loxosceles spider venoms

Vaccine. 2014 Apr 11;32(18):2086-92. doi: 10.1016/j.vaccine.2014.02.012. Epub 2014 Feb 22.

Abstract

We report the production of a neutralizing monoclonal antibody able to recognize the venoms of three major medically important species of Loxosceles spiders in Brazil. The mAb was produced by immunization of mice with a toxic recombinant L. intermedia sphingomyelinase D {SMases D isoform (rLiD1)} [1] and screened by enzyme-linked immunosorbent assay (ELISA) using L. intermedia, L. laeta and L. gaucho venoms as antigens. One clone (LiD1mAb16) out of seventeen anti-rLiD1 hybridomas was cross-reactive with the three whole Loxosceles venoms. 2D Western blot analysis indicated that LiD1mAb16 was capable of interacting with 34 proteins of 29-36kDa in L. intermedia, 33 in L. gaucho and 27 in L. laeta venoms. The results of immunoassays with cellulose-bound peptides revealed that the LiD1mAb16 recognizes a highly conserved linear epitope localized in the catalytic region of SMases D toxins. The selected mAb displayed in vivo protective activity in rabbits after challenge with rLiD1. These results show the potential usefulness of monoclonal antibodies for future therapeutic approaches and also opens up the perspective of utilization of these antibodies for immunodiagnostic assays in loxoscelism.

Keywords: Epitopes; Loxosceles spider venoms; Monoclonal antibody; Sphingomyelinases D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Neutralizing / immunology
  • Cross Reactions
  • Epitope Mapping
  • Epitopes / immunology*
  • Hybridomas
  • Mice
  • Mice, Inbred BALB C
  • Models, Molecular
  • Molecular Sequence Data
  • Neutralization Tests
  • Phosphoric Diester Hydrolases / immunology*
  • Rabbits
  • Recombinant Proteins / immunology
  • Spider Venoms / enzymology*
  • Spider Venoms / immunology
  • Spiders / enzymology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Epitopes
  • Recombinant Proteins
  • Spider Venoms
  • loxosceles venom
  • Phosphoric Diester Hydrolases
  • sphingomyelin phosphodiesterase D