ITHACA, N.Y. -- Results from the primary phase of the first-ever human clinical trial of an edible vaccine -- one that is genetically implanted inside a food -- indicate that consumption results in immunity to specific diseases. The test of the vaccine was made with servings of raw potatoes.
The initial findings are published in the May 1 issue of the journal "Nature Medicine". The vaccine-containing potatoes were developed at the Boyce Thompson Institute for Plant Research Inc. (BTI), an affiliate of Cornell University. The human clinical study was conducted under the direction of Dr. Carol Tacket at the University of Maryland School of Medicine's Center for Vaccine Development in Baltimore.
Scientists are hoping to wipe out enteric diseases, such as diarrhea and cholera, by using vaccines grown in specific foods that need no refrigeration. Potentially at stake in the two remaining phases of human clinical trials is the health of millions of children in developing nations.
Charles J. Arntzen, president of BTI, and Hugh S. Mason, a scientist at the institute, developed the edible vaccines and showed that uncooked vaccine-containing potatoes can trigger immune responses in animals. The potatoes were developed through a process known as transgenic implantation, in which a gene is transferred from one species to another. In this case the gene for a bacterial antigen -- the protein that stimulates the production of protective antibodies -- was inserted into the potato plant cells.
"The report in "Nature Medicine" documents the feasibility for both safety and usefulness of vaccines delivered in biotechnology-derived plants," Arntzen says.
In the first phase of human testing, the potatoes eaten by volunteers contained a vaccine against travelers' diarrhea, a common condition resulting from intestinal infection by the bacterium "E. coli", which contaminates food or water supplies. The clinical trials were approved in advance by the Food and Drug Administration.
American tourists commonly contract the bacterium in developing countries, but it is much more serious for the inhabitants of those countries. In fact, World Health Organization studies show that diarrhea caused by bacteria is a major cause of infant mortality worldwide, with nearly 3 million deaths a year. Yet there is no cost-effective vaccine available to prevent this problem, says Arntzen.
In the six-month, double-blind study, volunteers ate either 50 grams (1.75 ounces) or 100 grams (3.5 ounces) of genetically altered potatoes or regular potatoes. Each volunteer consumed three servings of potatoes over a three-week period. No significant side effects were reported.
Laboratory tests on blood and stool samples taken before and after the volunteers ate the potatoes were used to measure the vaccine's effectiveness. Antibody-secreting cells were found in the blood serum of the volunteers who ate the modified potatoes, and antibodies were found in both blood and stool samples.
Regina Rabinovich, M.D., the head of the National Institute of Allergy and Infectious Diseases' Vaccine and Treatment Evaluation Program, which is part of the National Institutes of Health, explains that high costs, transportation logistics and the lack of refrigeration for vaccines can thwart vaccination programs in these countries. "This trial is a milestone on the road to creating inexpensive vaccines that might be particularly useful in immunizing people in developing countries," she says. "The hope is that edible vaccines could be grown in many of the developing countries where they would actually be used."
In this first study, the researchers used a gene from "E. coli" that is similar to one from the bacterium that causes cholera. They anticipate that the vaccine may give cross-protection against both forms of diarrhea. Also under study for transgenic alteration are antigens of viruses such as the Norwalk virus, which causes severe epidemic outbreaks of viral diarrhea.
Potatoes are only a prototype for delivering plant-based vaccines. Techniques to create edible vaccines in bananas are now under way at BTI, but the crop takes much longer to mature and produce edible fruit. However, Arntzen says, these types of crops offer an "appropriate technology" for countries where vaccines are urgently needed.
A tasty vaccine-containing food, particularly bananas, a favorite food among children, could be inexpensive and plentiful. Delivery of vaccines in plant cells also may protect the antigen as it passes through the acid environment of the stomach.
Children of developing countries may not be the only beneficiaries of this new technology. Says Arntzen: "American kids will also probably prefer being vaccinated by an edible vaccine rather than by a needle."
BTI is a not-for-profit plant research institute founded in 1924 and has been affiliated with Cornell since 1974. It conducts research on plant biology and continues the tradition of using science and technology to protect the environment and improve human health and well-being.
Funding for the edible vaccine research came from the National Institute of Allergy and Infectious Diseases, part of the U.S. National Institutes of Health; the Thrasher Research Fund; the World Health Organization; and the National Science Foundation.
Journal
Nature Medicine