title: Neutralising antibodies against ricin toxin.
abstract: The Centers for Disease Control and Prevention have listed the potential bioweapon ricin as a Category B Agent. Ricin is a so-called A/B toxin produced by plants and is one of the deadliest molecules known. It is easy to prepare and no curative treatment is available. An immunotherapeutic approach could be of interest to attenuate or neutralise the effects of the toxin. We sought to characterise neutralising monoclonal antibodies against ricin and to develop an effective therapy. For this purpose, mouse monoclonal antibodies (mAbs) were produced against the two chains of ricin toxin (RTA and RTB). Seven mAbs were selected for their capacity to neutralise the cytotoxic effects of ricin in vitro. Three of these, two anti-RTB (RB34 and RB37) and one anti-RTA (RA36), when used in combination improved neutralising capacity in vitro with an IC(50) of 31 ng/ml. Passive administration of association of these three mixed mAbs (4.7 µg) protected mice from intranasal challenges with ricin (5 LD(50)). Among those three antibodies, anti-RTB antibodies protected mice more efficiently than the anti-RTA antibody. The combination of the three antibodies protected mice up to 7.5 hours after ricin challenge. The strong in vivo neutralising capacity of this three mAbs combination makes it potentially useful for immunotherapeutic purposes in the case of ricin poisoning or possibly for prevention.
authors.affiliation: CEA, iBiTec-S, Service de Pharmacologie et d'Immunoanalyse, CEA Saclay, Gif sur Yvette, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Prigent
authors.forename: Laetitia
authors.initials: L
authors.lastname: Panigai
authors.forename: Patricia
authors.initials: P
authors.lastname: Lamourette
authors.forename: Didier
authors.initials: D
authors.lastname: Sauvaire
authors.forename: Karine
authors.initials: K
authors.lastname: Devilliers
authors.forename: Marc
authors.initials: M
authors.lastname: Plaisance
authors.forename: Hervé
authors.initials: H
authors.lastname: Volland
authors.forename: Christophe
authors.initials: C
authors.lastname: Créminon
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Simon
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000493:pharmacokinetics / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D000915:Antibody Affinity / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D001667:Binding, Competitive / Q000276:immunology; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D019169:Jurkat Cells; D007785:Lactose / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D011041:Poisoning / Q000276:immunology / Q000517:prevention & control; D011485:Protein Binding / Q000276:immunology; D021122:Protein Subunits / Q000276:immunology; D012276:Ricin / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D020349:Surface Plasmon Resonance
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D021122:Protein Subunits; D012276:Ricin; D007785:Lactose