Protecting People from a Terrifying Toxin: Vaccine stimulates immune response against ricin

In its first test in people, a vaccine against the toxin ricin appears safe and generates antibodies that are expected to be protective against the potential bioterrorism agent.

Ricin comes from castor seeds and can cause lethal damage to the gut if swallowed or to the lungs if inhaled. Murderers and assassins have used it for centuries.

The vaccine might be used to protect soldiers and first responders in advance of possible ricin exposure, says immunologist and study leader Ellen S. Vitetta of the University of Texas Southwestern Medical Center in Dallas.

However, widespread vaccination “is going to be hard to justify,” argues Gary Nabel, director of the Vaccine Research Center at the National Institutes of Health in Bethesda, Md. Ricin poisonings are rare in people—fewer than 1,000 cases have ever been reported—and they usually result from accidental ingestion of castor seeds.

The Dallas researchers’ study is more interesting for its science than for its potential to mitigate ricin attacks, says Nabel. The “proof of concept” that the study represents could lead to new vaccines against numerous toxins, including those produced by staph and strep bacteria, he says.

For a mutant toxin to safely generate immunity, “you have to preserve the structures of the molecule that are seen by the immune system … at the same time that you modify specific amino acids that are responsible for its toxicity,” says Nabel. “This study shows that you can, in fact, do that.”

Vitetta and her colleagues developed the vaccine, called RiVax, by modifying the plant gene that makes part of the toxin. Like the natural ricin toxin, the altered protein stimulates the body to make antibodies. But it doesn’t kill cells. Antibodies against ricin can stop a poisoning only if they’re present before ricin exposure.

The researchers detected immune responses after giving three injections of the altered toxin to each of 15 healthy young adults. The team had previously shown that a similar response protects laboratory mice and rabbits against death after subsequent contact with ricin.

“The present study takes the research a step further by showing that humans can tolerate a dose that leads to the production of ricin-neutralizing antibodies,” says molecular cell biologist J. Michael Lord of the University of Warwick in England.

The vaccine produced, at worst, side effects that were mild and temporary, Vitetta and her collaborators report in an upcoming Proceedings of the National Academy of Sciences.

The antibody response observed should protect people, just as it protects animals, says Lord, who worked on a different experimental ricin vaccine until the British military stopped funding the research. The U.S. military is studying a third ricin-vaccine candidate.