Surprise discovery helps tackle rabies

Jan 5 2006

In an unexpected discovery, scientists at Jefferson Medical College have found that a tiny change in a rabies virus protein can turn a "safe" virus extremely deadly. The finding has enabled the researchers to refine a vaccine they previously created against rabies in wildlife, making it safer and more effective.

"We have identified a molecular mechanism involved in making the rabies virus pathogenic and lethal, and have developed a very safe vaccine for the immunization of wildlife," says Bernhard Dietzschold, DVM, professor of microbiology and immunology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, who led the work. "As a result, we think we have engineered a virus which is nonpathogenic and extremely stable."

Reporting recently in the Journal of Virology, Dr. Dietzschold, Matthias Schnell, Ph.D., associate professor of microbiology and immunology at Jefferson Medical College, and their co-workers identified a mutation in a rabies virus gene that changes a single amino acid in the virus's outer coat. The alteration was enough to turn a "safe" virus into a deadly version, making the virus unusable for vaccination.

Wildlife rabies is a substantial health problem in the United States. It is particularly prevalent along the East Coast, where more than 90 percent of reported cases occur in wildlife. Raccoons are the most affected, with skunks a close second. Worldwide--and especially in underdeveloped nations--rabies takes a large human toll; more than 60,000 deaths a year. In the United States alone, more than $1 billion is spent annually for control, treatment and prevention of rabies.

The Jefferson scientists uncovered the mutation, during the testing of a virus they thought was suitable for use in vaccinating wildlife. The virus is first altered so that it will not cause disease, yet will arouse the immune system's defenses. Because viruses such as rabies have high mutation rates, researchers typically "passage" the virus through mice. That is, they inject it into the animals, recover it, and then put into a second mouse. This is repeated at least five times. Five generations, Dr. Dietzschold explains, is usually enough to see whether the virus will either mutate and turn dangerous, or show genetic stability.

The research team has tested the current virus in 10 passages in mice, and it remained safe while retaining its potency. Dr. Dietzschold notes that the likelihood of a mutation occurring is extremely low. While different varieties of rabies virus exist, they maintain enough similarities in the all-important outer glycoprotein, that a vaccine that takes advantage of immune reactions to this protein can be effective.

Dr. Dietzschold explains that the current wildlife rabies vaccine used in the United States is ineffective in a chief carrier: skunks. The vaccine developed by his team is much broader, showing efficacy in such animals as raccoon, skunk and mongoose. One of the problems with current vaccines is the fact that several varieties are used, depending on the particular species of animal. The scientists hope their vaccine will prove useful for rabies prevention in several species.

The newer virus and vaccine currently are being evaluated by Molecular Targeting Technologies, Inc., of West Chester, Pa. The researchers are asking for permission from the United States Department of Agriculture and the Environmental Protection Agency to perform field trials. These would entail placing food baits containing the vaccine in the wild, then later capturing and testing animals for antibodies against the rabies virus.

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