A Ricin-Like Toxoid Used to Raise Goat Anti-Ricin Antibodies
Pp. 197-207 (11)
Donald I.H. Stewart, Erik J. Wiersma, Vadim Tsvetnitsky, Thor Borgford, Curtis Braun, Dominik Stoll, Veronica Restelli, John W. Cherwonogrodzky, Laurel M. Negrych and Charles C. Hu
A major difficulty in developing medical countermeasures against ricin (e.g.
passive antibody therapy) is the need to work with authentic ricin, a Schedule 1
Chemical under the Chemical Weapons Convention. Twinstrand Therapeutics Inc.
created a benign but antigenically intact variant of ricin by changing the genetic
sequence of the A and B chain linker peptide (representing less than 4% of the gene) to
block post-translational processing and activation. The toxoid protein, a single
polypeptide chain rather than dimer, was produced in a Pichia pastoris expression
system in accordance with Good Laboratory Practices (GLP). The toxoid was
determined to be 1000-fold less toxic than authentic ricin by both in vitro and in vivo
assays, allowing high immunogenic doses to be administered to test animals. Cangene
Corporation oversaw a contract in which goats were inoculated with varying schedules
and doses of the toxoid in accordance with GLP. DRDC Suffield Research Centre
assessed the activity of the resultant goat antibodies in challenges involving the wild
type toxin. The goat anti-toxoid antiserum was found to have high anti-ricin
neutralizing activity. The collaboration described was supported by the Defence
Research and Development Canada’s CBRNe Research and Technology Initiative
(CRTI) project 02-0007TA (2003-2005). All partners contributed generous In-Kind
Ricin, recombinant, toxoid, vaccine, immunoglobulin, anti-ricin,
Defence Research and Development Canada (DRDC), Suffield Research Centre, P.O. Box 4000, Station Main, Medicine Hat, AB, T1A 8K6, Canada.