Inhalation toxicology of ricin preparations: animal models, prophylactic and therapeutic approaches to protection

Abstract

Ricin is a toxin and seed protein produced by the castor oil plant, Ricinus communis. The toxin is a dimeric protein consisting of an enzymic A chain and a B chain with lectin properties aiding the uptake of the whole molecule into cells. Ricin has been considered a possible military threat for several decades and is now also of some concern as a terrorist agent. The inhalation route is of primary concern in these situations, although previous attacks with ricin have used other approaches. Medical countermeasures against ricin are urgently required and the strategy adopted has been first to understand the nature of the problem, in this case the inhalation toxicology of ricin, followed by the preparation of vaccine antigens. Toxoided ricin and modified recombinant A chain components have been examined in terms of efficacy as potential vaccine candidates in protection of animal models against inhaled ricin, primarily in laboratories both in the United Kingdom and in the United States. One recombinant A chain vaccine has been taken through to clinical trials in the United States and should become commercially available in the next few years. Toxoided ricin has also been used as an antigen to prepare antitoxin antibodies for therapeutic treatment following poisoning. In this review, a synopsis of the inhalation toxicology of ricin and approaches to medical prophylaxis and therapy of poisoning is given, based on work conducted at our laboratory and at other research institutes.