June 1, 1998
John Clements likes to joke these days that people are finally going to enjoy the "fruits of molecular biology." The Tulane University Medical Center microbiologist was part of a team of investigators who have shown that a genetically engineered potato can act like a vaccine in humans.
The groundbreaking report published in the May issue of Nature Medicine shows for the first time that an edible vaccine can safely trigger the bodyms disease-fighting mechanism. Using a principle developed and tested in animals by Clements and collaborators at Texas A&M University, the first phase of the test on humans began last fall in a double-blind trial at the University of Maryland.
Years earlier Clements and his team demonstrated that mice fed genetically altered plants produce protective antibodies to specific intestinal bacteria. Most microbiologists thought the same would not be true for humans. In the trial, 11 healthy adults were chosen at random to eat bite-sized pieces of genetically engineered raw potato.
The potato had been altered to contain antigens, which are substances that trigger antibody production against E. coli bacteria, the leading cause of bacterial diarrheal disease in developing countries. Three other volunteers ate pieces of raw, ordinary potato. Blood and stool samples periodically collected from volunteers in the trial were evaluated to determine the vaccinems ability to stimulate both blood-borne and mucous immune responses.
Ninety percent of the volunteers who ingested the altered potatoes had antibodies in their blood and more than 50 percent had fecal antibodies, Clements says. This proof that edible vaccines work on humans is another brick in building a pyramid to a successful edible vaccine, Clements says.
"New and improved vaccines and novel ways of delivering them are crucial to reducing the burden of infectious diseases," says Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, which supported the study that also involved collaborators in Baltimore and Ithaca, N.Y.
Each year infectious diseases kill 17 million people, including 9 million children, Fauci says. Most of these deaths are in developing countries where public health systems and sophisticated waste and water treatment are virtually nonexistent.
Even the cost of immunizations is out of reach for many of these countries. When a country cannot afford to pay 10 cents for a packet of oral rehydration medicine to combat diarrhea, the $90 price tag for three doses of the rotavirus vaccine for bacterial diarrhea is certainly out of the question, Clements says.
"Even if a vaccine does exist, if they can't afford it, itms a non-starter. It doesnmt make any difference," he says.
That's where the edible vaccine comes in. Researchers are touting it as a viable option in developing countries because it is less expensive and readily available. A potato, even one that is genetically altered, costs only pennies to produce and grows almost anywhere. Although the potatoes were well-tolerated by volunteers in the trial, not many adults or children get excited about munching a raw spud. Because antigens do best in a liquid environment, the high water content and rapid growth of potatoes made them a logical choice for the initial test.
However, bananas and tomatoes also are inexpensive to grow and eating them raw is much more appealing. Clements' team is already at work on a genetically altered banana.
"It costs about three cents to grow one banana in a third world country, most of which are tropical anyway," he says. "One banana could make as many as 10 vaccination doses. That's what's so important about edible vaccines: It's affordable and we've proved it's medically effective."
He envisions a time in the not-too-distant future when a truck from the World Health Organization, or some other philanthropic group, drives up to a village and workers start handing out banana chips as a form of immunization.
"It is a potential vaccine delivery system in areas of the world where high-tech molecular biology is not appropriate," Clements adds. "Now you don't have to have a sophisticated molecular biology setup to produce the antigen. All you have to have is a patch of ground and a will."
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