DALLAS – Sept. 4, 2002 – UT Southwestern Medical Center at Dallas researchers have developed a vaccine in mice against the deadly toxin ricin. Ricin has been used as a biological weapon in many parts of the world.
"Ricin is not only dangerous, but it is also cheap and easy to make," said Dr. Ellen Vitetta, director of the Cancer Immunobiology Center at UT Southwestern and senior author of the study to be published in the Sept. 10 issue of the journal Vaccine.
Large stockpiles of ricin have been found in several countries in the Middle East, Vitetta said. It is a protein produced by castor beans. A single ricin molecule inside a cell shuts down protein synthesis, killing the cell. Ricin can be administered in foods and water or sprayed as an aerosol. A small dose can produce flulike symptoms and result in death in a few days.
Because of its ease of production and high toxicity, ricin has found its way into the arsenals of extremist individuals, groups and governments. Iraq is known to have ricin as part of its biological weapons program, and it is believed that at least one group linked to the terrorist organization al-Qaeda also has experimented with the poison as a weapon. Domestically, several individuals have been arrested and convicted of ricin possession in recent years under the 1989 Biological Weapons Antiterrorism Act.
In creating the new vaccine, UT Southwestern researchers, led by Vitetta, mutated the DNA encoding the active A chain of the toxin. They took out the site that inhibits protein synthesis, as well as the site responsible for inducing vascular leak. The latter was identified by Vitetta's group several years ago in its ongoing efforts to produce safer immunotoxins containing the A chain. Immunotoxins are anti-cancer drugs that have been used by Vitetta and her colleagues in more than 200 cancer patients. The new recombinant A chain induces a protective immune response in mice and protects them against very high doses of ricin. There were no vaccine-related side effects.
The UT Southwestern scientists created three recombinant versions of ricin A chain, two of which were effective as vaccines in mice. Vitetta said E. coli bacteria are used to produce the recombinant DNA, making vaccine production cheap and safe. The researchers believe one or both of the vaccines would be safe and effective in humans.
Vitetta said tests against airborne ricin will be initiated as soon as the experiments can be safely done in a biosafety level 3 facility, which is currently in the planning stage.
Once immunized mice have been subjected to an aerosol challenge, the next step would be to optimize production, formulation and storage of the vaccine. Then 10 human volunteers would be vaccinated. Their sera would be injected into mice and tested for its ability to protect mice from ricin aerosols.
Vitetta said a large government agency, such as the Army or National Institutes of Health, or a well-funded private company would then have to step in and take the vaccine through clinical trials. Such trials are well beyond our resources, she said.
"We have only tested it against injected ricin, but, based on past experience, there's every reason to believe it will be protective against aerosolized ricin," Vitetta said.
Ricin was used in the 1978 murder of Georgi Markov, a Bulgarian author and dissident. Markov, who had defected nine years earlier, was assassinated while waiting for a bus in London when he took an apparently accidental poke from another man's umbrella. Four days later Markov was dead, and it was only upon autopsy that ricin poisoning was revealed as the cause. The lethal dose, estimated at 450 micrograms, was delivered in a pinhead-sized hollow pellet, discovered during the autopsy.
The Centers for Disease Control and Prevention ranks ricin on its "B" list of biowarfare or bioterrorist agents – placing it in the category of a moderate threat.
Other contributors to the Vaccine study, all from the Cancer Immunobiology Center, were first author Dr. Joan E. Smallshaw, postdoctoral researcher; research assistants Ana Firan, John R. Fulmer, Stephen L. Ruback; and Dr. Victor Ghetie, professor.
The work was supported by a National Institutes of Health grant.
Materials provided by University Of Texas Southwestern Medical Center At Dallas. Note: Content may be edited for style and length.
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