Insertional mutagenesis of ricin A chain: a novel route to an anti-ricin vaccine

Vaccine
Catherine J MarsdenJ M Lord

Abstract

The insertion of a specific 25-residue internal peptide into ricin toxin A chain (RTA) reduced the catalytic activity of this protein approximately 300-fold. Directed proteolytic cleavage of the peptide insert essentially restored catalytic activity of the resulting two peptide A chain to normal levels. Ricin holotoxin containing unprocessed mutant A chain was not toxic to cultured mammalian cells, due to enhanced proteasomal degradation, nor was it toxic when injected into rats at a concentration that is lethal in the case of native ricin. Rats treated in this way were completely resistant to native ricin when subsequently challenged with a potentially lethal dose of the toxin. These ricin-resistant animals had a significant anti-ricin antibody titer, indicating that this approach has potential for developing an effective vaccine against this toxin.

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Citations

Feb 8, 2006·Proceedings of the National Academy of Sciences of the United States of America·Ellen S VitettaJohn Schindler
May 14, 2005·Expert Review of Vaccines·Catherine J MarsdenJ Michael Lord
Sep 29, 2004·Toxicon : Official Journal of the International Society on Toxinology·Lynne M Roberts, Daniel C Smith
May 28, 2011·Toxicon : Official Journal of the International Society on Toxinology·Aimee PorterLuis DaSilva
Jun 7, 2005·Advanced Drug Delivery Reviews·Vincent W BramwellH Oya Alpar
Dec 9, 2014·Human Vaccines & Immunotherapeutics·Tao ZhangJinglin Wang
Nov 10, 2011·Toxins·Seth H PincusEllen S Vitetta

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