"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
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
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.
Arntzen CJ. Pharmaceutical foodstuffs-oral immunization with
transgenic plants. Nature Medicine (vaccine supplement)
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
Press releases, fact sheets and other NIAID-related materials are
available on the NIAID Web site at http://www.niaid.nih.gov.