January 1997
A
banana a day may keep diseases away.
ITHACA, N.Y. — Someday vaccinations could be as simple and painless as eating a banana. That would mean no more crying children, and no more adverse events like redness, swelling and fussiness commonly associated with administering vaccines.
Plant molecular biologist Charles Arntzen, PhD, president and chief executive officer of the Boyce Thompson Institute for Plant Research, has been researching edible vaccines since the fall of 1991. He discovered that foreign genes can be inserted into banana DNA. Arntzen and his colleagues are currently in the process of applying to the Food and Drug Administration (FDA) for authorization to conduct human trials using the "banana vaccine."
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Studies so far have proven tobacco plants can be engineered to produce the hepatitis B surface antigen. The plant antigen strongly resembles that used in the current recombinant hepatitis B vaccine. Mice inoculated with leaf extracts from the plants show the full immune response seen in humans vaccinated with the hepatitis B vaccine.
Potatoes produced an antigen of enterotoxic Escherichia coli ETEC) responsible for numerous cases of diarrheal disease in developing countries, and mice showed immunity to the antigen after eating the raw potatoes. The Norwalk virus, another common cause of diarrhea, has also been used in experiments, but no other vaccines are currently being tested in plants, said Arntzen, adjunct professor of biological science at Cornell University.
"This is very expensive work, and we've decided to demonstrate success in these systems as a first step," he said.
Purification for viral contaminants wouldn't be necessary with plant vaccines since plant viruses can't infect humans.
Another advantage, he said, is that plant vaccines wouldn't need costly refrigeration; the plants could be grown where the vaccines are used, which illustrates another advantage.
"Plants can be grown anywhere cheaply," Arntzen said.
The plants would be genetically engineered to carry genes from disease-causing microbes. Within the microbes, these genes control production of molecules, or antigens, known to provoke an immune response in those infected with the microbes. Once inside the plant's genetic DNA, the genes force the plant to produce the vaccinating antigens.
Arntzen estimates needing approximately 20,000 tons of bananas to vaccinate all the world's children, which he says is only a fraction of the 9 million tons of bananas produced worldwide each year. Growing fields of them should be a cheaper source of vaccine than the microbial fermenters used in today's vaccine production facilities. One banana can potentially contain 10 doses of vaccine, he said.
Arntzen said they currently have small plants with vaccine genes that are prototypes, but it will take approximately two years for them to produce the first fruit, he said. The fruit must then be tested in animals first.
According to Arntzen, "it will be at least five years," until the first banana-based vaccine will be available because of the time it takes for the plant to grow.
Arnzten said they've also engineered potatoes to produce an antigen of a particularly toxic form of Escherichia coli that affects many in developing countries. Although it takes approximately two months to produce a potato with this vaccine, the potatoes must also be eaten raw because heat inactivates the protein antigens, making it less appetizing to babies.
Advantages to using plant vaccines include multiple target diseases, oral administration and induction of mucosal immunity, which are the three priorities of the Children's Vaccine Initiative (CVI).
If the early findings in mice are borne out in human trials, plant vaccines should be capable of stimulating not only the more general antibody and cellular immunity needed for protection against most disease-causing microbes, but also mucosal immunity, which is probably the ideal, first-line defense against many diarrhea-causing microbes, Arntzen said.
This technology is not new, he said, because today there are more than 40 different species of genetically engineered food, many of them being tested for human consumption. The first successful splicing of plant DNA was in 1983.
However, there are vaccines that plants won't be able to produce like the conjugate vaccines which get their strong immunogenicity by linking an antigen to an immunogenic protein through a fairly complex biochemical conjugation process.
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