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Protein vaccine fully protects mice from lethal aerosol challenge with ricin toxin

Scientists have developed an experimental vaccine against ricin, a potential biological threat agent, which fully protected mice from aerosol challenge with lethal doses of the toxin. The study was performed at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID).

Ricin is a toxin derived from the castor plant, which is grown throughout the world for commercial purposes. Approximately one million pounds of castor beans are used each year in the process of manufacturing castor oil.

When inhaled as a small-particle aerosol, ricin produces severe respiratory symptoms followed by respiratory failure within 72 hours. When ingested, ricin can cause severe gastrointestinal symptoms followed by vascular collapse and death.

Given its ready availability and its high level of toxicity--particularly when delivered as an aerosol--ricin is a significant potential agent of biological warfare or terrorism. Currently, there is no vaccine or therapy available for human use.

According to lead investigator Mark A. Olson, Ph.D., ricin is composed of two different protein subunits called the A-chain and the B-chain. The ricin B-chain (RTB) binds the toxin to the cell surface, an interface that is essential for the ricin A-chain (RTA) to enter the cell. Once inside the cell, RTA effectively stops new protein synthesis and causes cell death.

Previous attempts to develop a ricin vaccine suggested that isolated RTA could induce protective immunity against the toxin in animals. However, using RTA as a vaccine component was problematic because it was not stable--it failed to maintain its structural integrity when heated or placed in solution, resulting in clumping and separation. The safety and efficacy of a vaccine depend upon the stability of its formulation.

The new vaccine candidate, called RTA 1-33/44-198, is a fragment of the ricin A-chain that has been modified to eliminate the toxic enzymatic prope
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Contact: Caree Vander Linden
Caree.Vander-Linden@amedd.army.mil
301-619-2285
US Army Medical Research Institute of Infectious Diseases
4-Aug-2004


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