"A big stash of ricin was found in the caves of Afghanistan," says Ellen Vitetta of the University of Texas Southwestern Medical Center in Dallas, whose team developed the vaccine. "They weren't collecting it to make stew."

Ricin, a natural toxin found in castor beans, is cheap and relatively easy to produce. And as it is a powder, it is easily turned into an aerosol that can be inhaled.

Nor does it take much to kill someone: just 1 to 10 micrograms of ricin per kilogram of body weight. About this amount on the sharpened tip of an umbrella was enough to kill the Bulgarian dissident Georgi Markov, after an infamous attack on London's Waterloo Bridge in 1978.

"You get flu-like symptoms, then suddenly you're dead," says Vitetta. "This stuff really frightens me."

Fluid retention
 

The toxin has two components. Its "B chain" binds to cells, allowing the second component, the "A chain", to enter the cell and disable the protein factories. Just a single A chain can kill a cell.

The team's vaccine, which is a stripped-down version of the A chain, arose as a spin-off from Vitetta's work on ricin-based anti-cancer drugs. The idea, which many groups are working on, is to attach the A chain to antibodies that target tumour cells.

In trials, however, Vitetta found that while the ricin-based drugs do kill cancer cells, patients given high doses can develop a side effect called vascular leakage. "They retain fluid, gain weight and can have organ failure," Vitetta says.

To improve the anti-cancer drugs, Vitetta and her colleagues stripped out the part of the toxin that was causing vascular leakage. "Then we thought: why don't we make a vaccine by stripping out the active site, too."

Army interest
 

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Weblinks

University of Texas Southwestern Medical Center

Ricin, Texas Department of Health

National Institutes of Health

Bioterrorism, New Scientist

Vaccine

Of the three versions of the A chain they genetically engineered, two turned out to have the desired effect on mice. The animals survived exposure to 10 times the dose of ricin that killed unvaccinated mice.

"It's cheap, simple and protects wonderfully without side effects because it's a totally inactive protein," Vitetta says. She has now applied to the National Institutes of Health for further funding to test the vaccine against aerosolised ricin and hopes eventually to test the vaccine in people.

The US Army is also interested because no approved vaccine exists. Previous attempts to make one by chemically inactivating the toxin failed.

Journal reference: Vaccine (vol 20, p3422)

Andy Coghlan

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