Jefferson Scientists Develop Botulism Vaccine

November 07, 1997

Molecular biologists at Thomas Jefferson University, Philadelphia, have created an oral vaccine against botulism. The researchers believe that such a vaccine could be used as a prototype in developing future vaccines for other diseases such as diphtheria, whooping cough and tetanus. Eventually, they say, their discovery may lead to a range of oral vaccines that could be inserted into common foods.

Lance Simpson, Ph.D., professor of medicine, Jefferson Medical College, and director of the Jefferson Clinical Center for Occupational and Environmental Medicine, and his colleagues, Nikita Kiyatkin, Ph.D., and Andrew Maksymowych, Ph.D., used the sophisticated tools of molecular biology to create a modified and non-toxic version of botulinum toxin, which is nature’s deadliest poison. The toxin, which is the cause of the disease botulism, is ordinarily encountered as a form of food poisoning. When someone ingests the toxin, it survives the harsh conditions of the gastrointestinal (GI) system and moves into the general circulation. It is eventually delivered to the central nervous system and causes paralysis.

The researchers have created a novel form of the toxin that retains the ability to survive the GI system and enter the general circulation, yet no longer can poison nerves. As a result, the novel molecule is an effective oral vaccine against botulism. The scientists, reporting in November in the journal Infection and Immunity, detail the results of experiments in which they successfully immunized mice against botulism.

One immediate use of a botulism vaccine, Dr. Simpson notes, would be in veterinary medicine. Animals such as racehorses and farmyard chickens are susceptible to the disease, making such a vaccine of interest to the pharmaceutical industry.

According to Dr. Simpson, there may be far greater applications of the work in both veterinary and human medicine.

“The very properties that this molecule possesses are the ones that would be essential for all oral vaccines,” he explains. “The molecule could be used as a carrier to transport other potential vaccines from the gastrointestinal system into the general circulation, where they would evoke antibodies. If this were to work, the novel carrier molecule could be the critical element needed to create a host of new oral vaccines.”

One use of this vaccine technology would be for common diseases such as diphtheria and tetanus. Dr. Simpson sees a possibility for an even more intriguing use.

“There are Third World countries in which injectable or even oral vaccines are still not practical; the health systems and finances are inadequate,” he explains. “What might be a more practical solution is to put the genes for the carrier-vaccines into a plant such as a banana. As the banana grows, it would automatically synthesize the oral vaccines. Whenever a person ate the banana, that person would also be consuming oral vaccines. This might be a way to combat illnesses that are endemic to some parts of the developing world.”Dr. Simpson and his colleagues are now constructing the genes that will encode the carrier-vaccine molecules. They will test the ability of the molecules to act as oral vaccines in the laboratory. If the work is successful, the next step will be to conduct human trials.
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Thomas Jefferson University

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