Plant-based expression of a partially humanized neutralizing monoclonal IgG directed against an immunodominant epitope on the ricin toxin A subunit

Vaccine. 2012 Feb 8;30(7):1239-43. doi: 10.1016/j.vaccine.2011.12.058. Epub 2011 Dec 22.

Abstract

GD12 is a murine monoclonal IgG(1) (mAb) that recognizes an immunodominant linear neutralizing epitope (163-TLARSFIICIQM-174) on the A subunit (RTA) of ricin toxin. With the long-term goal of using GD12 as a potential countermeasure against ricin intoxication, we have produced a chimeric derivative of GD12 (cGD12) in which the murine heavy and light chain variable regions were fused to a human IgG(1) framework. The chimeric mAb, expressed and purified using a Nicotiana-based system demonstrated epitope specificity and ricin neutralizing activity similar to the parental murine mAb. Passive administration of cGD12 (10μg) to mice by intraperitoneal injection protected the animals against a systemic ricin challenge. In a post-exposure setting, the murine and chimeric mAbs administered as much as 6h after toxin challenge were each capable of rescuing mice from toxin-induced death, revealing the potential of GD12 to serve as both a prophylactic and therapeutic for ricin intoxication.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / biosynthesis
  • Antibodies, Monoclonal, Humanized / genetics
  • Antibodies, Neutralizing / administration & dosage*
  • Antibodies, Neutralizing / biosynthesis
  • Antibodies, Neutralizing / genetics
  • Epitopes
  • Female
  • Gene Expression
  • Humans
  • Immunization, Passive
  • Immunodominant Epitopes
  • Immunoglobulin G / chemistry
  • Immunoglobulin G / immunology*
  • Injections, Intraperitoneal
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Poisoning / prevention & control
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / genetics
  • Ricin / immunology*
  • Ricin / toxicity
  • Tobacco / genetics
  • Tobacco / metabolism*

Substances

  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neutralizing
  • Epitopes
  • Immunodominant Epitopes
  • Immunoglobulin G
  • Recombinant Fusion Proteins
  • Ricin