RiVax™ (Ricin toxine vaccine)

What is Ricin Toxin?

Ricin toxin is a protein derived from the beans of the castor plant (Ricin communis). The toxin is a waste byproduct from the production of castor oil.

What are the Effects of Exposure to Ricin Toxin?

Ricin is extremely toxic; the lethality is dependent to a large degree on the route of exposure. The amount of ricin that would fit onto the head of a pin would be lethal to an adult if injected into the blood stream. Roughly the same amount would kill an adult if properly aerosolized and inhaled. A slightly larger amount (approximately 10 times) would be necessary to kill if the toxin was ingested.

Ricin toxin works by irreversibly binding to, and entering, cells in the body that the toxin comes into contact with. Once inside the cell, the toxin inhibits protein synthesis which leads to cell death. One molecule of ricin toxin is enough to destroy a single cell. If ricin is injected into the blood stream, it can cause severe local necrosis of the muscle and regional lymph nodes with organ involvement and rapid death. If ricin is inhaled into the lungs, it will cause severe respiratory distress and death within 36-72 hours. When a large enough amount is ingested, ricin toxin causes severe gastroenteritis, bleeding of the gastrointestinal tract, and necrosis of the liver, kidney, and spleen, leading to death within a few days. e

How Is Ricin Poisoning Treated?
There is no known treatment or vaccine available for ricin poisoning. Ricin poisoning is treated by supportive care only.

Why is Ricin Considered a Bioterror Threat?

Ricin is extremely deadly in small doses. Ricin beans are widely available and the toxin is easy and inexpensive to produce. The toxin is stable in powder and aerosolized form, can be disseminated as an aerosol, an injection, or as a food or water contaminant, and has no known treatment or vaccine. The availability, ease of manufacture, and lethality make it an attractive bioterror or biowarfare weapon.

Has Ricin Toxin Been Used as a Weapon Before?

Yes, and evidence is suggesting that it’s appeal as a weapon is increasing in the U.S. and abroad.
In the U.S. there have been 5 instances of ricin-related threats since 1991. On January 12, 2003, the FBI issued a nationwide alert to 17,000 law enforcement agencies as well as food and beverage processors and suppliers across the U.S. to be on the lookout for use of ricin as a contaminate. The CDC began a daily ricin watch in November, 2003 after ricin was found in an airport mail center in Greenville, NC. The most recent case resulted in the closing of three U.S. Senate office buildings on February 3rd, 2004 after ricin was found in U. S. Senator Bill Frist’s mailroom.

A recent article published in the Washington Post (May 5, 2004) reported that evidence is mounting that al Qaeda is experimenting with manufacturing ricin for the purposes of using it as a bioterror weapon. French authorities, who are investigating an al Qaeda chemist in Lyon, France, recently discovered that he had been producing jars of ricin in his apartment; the number and whereabouts of these jars is unknown and of great concern to the French government amid rising speculation of future bioterror attacks in Europe. Ricin-making equipment or evidence of the toxin has been identified in al Qaeda-related cells in Britain, France, Spain, Russia, Georgia and northern Iraq in the past 2 ½ years. Materials seized from al Qaeda members recently included terrorist manuals with detailed instructions on how to manufacture and use ricin toxin.

Perhaps the most famous ricin poisoning case was that of dissident Bulgarian writer Georgi Markov and what’s commonly known as the “Umbrella Assassination.” Markov was a controversial political author and playwright who was forced to flee communist Bulgaria in 1969 after warnings that his life may be in danger. Markov spent the next 10 years living in various European countries and finally settled in London. On September 7, 1978, Markov was waiting at a bus stop when he experienced a sudden stinging pain in the back of his right thigh. He turned and saw a man bending to pick up a dropped umbrella, the tip of which had poked Markov in the back of the right thigh. Later that evening, Markov developed a high fever and was taken to a hospital, where he was treated for an undetermined form of blood poisoning. He went into shock, and after three days of agony, he died. During the post-mortem, a 1.52 mm pellet was excised from the wound in the back of his thigh and the British government chemical defense group at Porton Down determined that it had contained ricin toxin, the source of Markov’s death.

About RiVax™

In September 2002, DOR BioPharma, Inc. executed an exclusive, worldwide licensing agreement for the rights to an experimental ricin vaccine (RiVax) from the University of Texas Southwestern Medical Center (UT Southwestern). The vaccine, which is being developed in collaboration with UT Southwestern, is a modified subunit of the native ricin toxin which has been genetically engineered to eliminate both its enzymatic activity and its ability to induce vascular leak syndrome (VLS). Complete elimination of both types of toxicity is likely to render this vaccine safe at effective doses and when administered as an intramuscular injection, RiVax induces protective antibody production in mice (Smallshaw et al. 2002. Vaccine. 20:3422-27).

In parallel to the development of this intramuscular vaccine, we are testing a variety of vehicles incorporating RiVax for nasal administration. The rationale for a nasally-administered ricin vaccine are two-fold: a) Convenience in the event that a large number of people require vaccination in a short period of time, and b) ricin toxin can destroy any cells it comes into contact with, increasing the need for protection of exposed mucosal surfaces. Since likely routes of exposure to the toxin include inhalation or ingestion, protecting the mucosal lining of the lungs and gut is important. Preclinical experiments are ongoing to determine whether a nasal formulation is stable and capable of conferring mucosal immunity.