Ricin vaccine effective in mice

Engineered molecule could protect against bioterrorism attack. | By Laura DeFrancesco

Researchers at the University of Texas Southwestern Medical School report in the 10 September issue of Vaccine that an engineered ricin vaccine protects mice against ricin's toxic effects while being non-toxic itself. Previous attempts to make ricin vaccines have failed because of toxicity. The U.S. Centers for Disease Control (CDC) considers ricin a class B bioterrorism agent.

Ricin is a potent toxin, which kills by eliminating the protein synthetic capability of a cell. A single molecule of the ribotoxic A chain can kill a cell; an extremely low dose can kill a human. Ricin's reputed use in espionage is difficult to prove since the molecule is lethal at undetectable doses. However, in one famous Cold War assassination, Bulgarian dissident Georgi Markov died in London after being pricked by an umbrella. A pellet in the umbrella tip was later discovered to contain ricin.

In July 2002, CIA and Pentagon observers reportedly witnessed animal experiments involving ricin being conducted by Al Quaeda operatives in Northern Iraq.

The ricin vaccine is an outgrowth of twenty years of work by Ellen Vitetta and colleagues at Southwestern Medical School on immunotoxins-hybrid molecules that couple specific antibodies to ricin's A chain. An immunotoxin against lymphoma that Vitetta's group has been developing kills tumor cells in cancer patients, but it also has some serious side effects. By removing a single amino acid, Vitetta's group has been able to eliminate the side effects.

It struck her one day, Vitetta said, that by removing the active site, they might have something that would vaccinate. "If that works, we've got a totally non-toxic vaccine against a very toxic poison. Nobody's been able to do that. It was one of those, 'let's try it,'" she recalled. They removed the active site and the key amino acid in the site that induced problems in patients. Immunizing mice with this molecule provided protection against injected ricin at 10 times its LD50 with no side effects.

The next step is to see if the vaccine protects against ricin administered to mice by other routes, particularly by aerosol, one likely path that terrorists might use. Following that, Vitetta intends to test the vaccine's ability to induce protective antibodies in humans. She plans to immunize a cohort of human volunteers and see if their antiserum protects mice against ricin-passive immunity. For Vitetta, that would be sufficient proof that the vaccine works. "If it protects passively, it will protect actively," she said.

Vitetta is in discussions with the U.S. Department of Defense about using the vaccine to protect the armed forces. "The problem [with ricin] is that the symptoms are not notable. You couldn't look at someone and say, 'you have received ricin.' Nothing spectacular happens -They feel lousy, flu-like and then they're gone," she said. "The army's view [of the vaccine]," Vitetta explained, "is to get it into all the soldiers."