First Human Trial Shows That An Edible Vaccine Is Feasible

"Edible vaccines offer exciting possibilities for significantly reducing the burden of diseases like hepatitis and diarrhea, particularly in the developing world where storing and administering vaccines are often major problems," says Anthony S. Fauci, M.D., director of NIAID.

The Phase 1 proof-of-concept trial began last fall at the University of Maryland School of Medicine's Center for Vaccine Development under the direction of Carol O. Tacket, M.D., professor of medicine.

The goal of the study was to demonstrate that an edible vaccine could stimulate an immune response in humans. Volunteers ate bite-sized pieces of raw potato that had been genetically engineered to produce part of the toxin secreted by the Escherichia coli bacterium, which causes diarrhea.

Previously, NIAID-supported in vitro and preclinical studies by John Clements, Ph.D., and colleagues at Tulane University School of Medicine showed that transgenic potatoes containing this segment of the toxin stimulated strong immune responses in animals. The transgenic potatoes were created and grown by Charles Arntzen, Ph.D., and Hugh S. Mason, Ph.D., and their colleagues at the Boyce Thompson Institute for Plant Research, an affiliate of Cornell University.

The trial enrolled 14 healthy adults; 11 were chosen at random to receive the genetically engineered potatoes and three received pieces of ordinary potatoes. The investigators periodically collected blood and stool samples from the volunteers to evaluate the vaccine's ability to stimulate both systemic and intestinal immune responses. Ten of the 11 volunteers (91 percent) who ingested the transgenic potatoes had fourfold rises in serum antibodies at some point after immunization, and six of the 11 (55 percent) developed fourfold rises in intestinal antibodies. The potatoes were well tolerated and no one experienced serious adverse side effects.

Encouraged by the results of this study, NIAID-supported scientists are exploring the use of this technique for administering other antigens. Edible vaccines for other intestinal pathogens are already in the pipeline--for example, potatoes and bananas that might protect against Norwalk virus, a common cause of diarrhea, and potatoes and tomatoes that might protect against hepatitis B.

Regina Rabinovich, M.D., oversees NIAID's Vaccine and Treatment Evaluation Program, of which the University of Maryland's vaccine center is a part. "This first trial is a milestone on the road to creating inexpensive vaccines that might be particularly useful in immunizing people in developing countries, where high cost and logistical issues, such as transportation and the need for certain vaccines to be refrigerated, can thwart effective vaccination programs," she comments. "The hope is that edible vaccines could be grown in many of the developing countries where they would actually be used."

***Details of the Study***

The study nurse at the University of Maryland peeled the potatoes just before they were eaten, because potato skin sometimes contains a compound that imparts a bitter taste and can cause nausea and stomach upset. The potatoes were then cut into small, uniform pieces and weighed into 50-gram and 100-gram doses. Each person received three doses of either 50 grams or 100 grams of potato over a three-week period, at 0, 7 and 21 days. The dosage size varied in order to evaluate any side effects from eating raw potatoes.

NIAID is a component of the National Institutes of Health (NIH). NIAID conducts and supports research to prevent, diagnose and treat illnesses such as AIDS and other sexually transmitted diseases, malaria, tuberculosis, asthma and allergies. NIH is an agency of the U.S. Department of Health and Human Services. ###

References:

Arntzen CJ. Pharmaceutical foodstuffs-oral immunization with transgenic plants. Nature Medicine (vaccine supplement) 1998;4(5):502-03.

Haq TA, Mason HS, Clements JD, and Arntzen CJ. Oral immunization with a recombinant bacterial antigen produced in transgenic plants. Science 1995;268:714-16.

Mason HS, Haq TA, Clements JD, and Arntzen CJ. Edible vaccine protects mice against E. coli heat-labile enterotoxin(LT): potatoes expressing a synthetic LT-B gene. Vaccine, In Press.

Tacket CO, Mason HS, Losonsky G, Clements JD, Levine MM and Arntzen CJ. Immunogenicity in humans of a recombinant bacterial antigen delivered in a transgenic potato. Nature Medicine 1998;4(5):607-09.

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