http://www.newscientist.com/news/print.jsp?id=ns99992783
NewScientist.com
Vaccine developed for lethal ricin
10:31 12 September 02
Andy Coghlan
A vaccine against the lethal toxin ricin could soon be available - and it
may be needed, researchers warn.
"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
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)
10:31 12 September 02
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R. A. Hettinga