title: Plant-based expression of a partially humanized neutralizing monoclonal IgG directed against an immunodominant epitope on the ricin toxin A subunit.
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.
authors.affiliation: Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, NY 12208, United States.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: O'Hara
authors.forename: Kevin
authors.initials: K
authors.lastname: Whaley
authors.forename: Michael
authors.initials: M
authors.lastname: Pauly
authors.forename: Larry
authors.initials: L
authors.lastname: Zeitlin
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Mantis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D057134:Antibodies, Neutralizing / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D000939:Epitopes; D005260:Female; D015870:Gene Expression; D006801:Humans; D007116:Immunization, Passive; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology*; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011041:Poisoning / Q000517:prevention & control; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics; D012276:Ricin / Q000276:immunology* / Q000633:toxicity; D014026:Nicotiana / Q000235:genetics / Q000378:metabolism*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D000939:Epitopes; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D012276:Ricin