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Rockefeller Foundation provides grant to Boyce Thompson Institute at Cornell to begin technology transfer of oral vaccine

Researchers at the Boyce Thompson Institute for Plant Research Inc. at Cornell University now will begin exchanging information with scientists in developing countries, beginning with Mexico, on vaccines that are easier to deliver, thanks to a new Rockefeller Foundation grant.

Traditional vaccines that inoculate children against enteric diseases, such as diarrhea and cholera, are very expensive to send to developing countries. Arntzen and BTI researchers are developing genetically changed foods that are grown with the vaccine already in them as a cheap and easy way to deliver vaccines to children throughout the world. For example, the BTI researchers are working on genetically installing some oral vaccines into bananas.

"This clears the way for international technology transfer of our oral vaccines," said Charles J. Arntzen, president of Boyce Thompson Institute (BTI). "This grant is an endorsement and it has become a first step in the process of bringing our research to people who need it."

Specifically, the three-year Rockefeller Foundation grant will enable Miguel Gomez-Lim, of the Centro de Investigacion y de Estudios Avanzados del I.P.N. (CINESTAV), Mexico City, a government health research agency, to collaborate with BTI researchers.

Gomez-Lim, the lead scientist from the Mexican side, will spend part of the next three years in Ithaca helping to develop delivery techniques for vaccines against diarrhea -- which are needed to reduce infant mortality in his country.

Gomez-Lim and his American colleagues will try to verify the value of "edible" vaccines by designing experiments to be conducted in parallel in the two countries. They also will begin educational and human clinical efforts in Mexico to facilitate the rapid adoption of these vaccines for safe and effective use.

"The goal is to deliver a 'technology package' which makes the eradication of one or more infectious diseases possible -- on a global scale," Arntzen said. While work progresses on the vaccines for enteric diseases, Arntzen hopes that this research eventually will lead to an oral HIV vaccine delivered in a food product that can be used cost-effectively around the world as an inoculation against AIDS.

In 1995, BTI researchers first showed that oral vaccines work in animal tests, by feeding animals raw potatoes that had been modified to include a vaccine agent. Human clinical trials are now being planned that will use the same type of genetically changed raw potatoes.

Enteric, or diarrheal diseases, kill more children in many developing countries than any other diseases. For children under age 5 in developing countries, one-third of deaths are from these types of illnesses. Almost 25 percent of children who die between the ages of 5 and 14 lose their lives to enteric illnesses. These diseases account for between 3 and 5 million children's deaths annually, and many could be prevented if such inexpensive and easily used vaccines were available.

"If less expensive vaccines were available that can be produced in countries that need them, they would have an immediate impact around the world," Arntzen said. "A crop can be made to produce edible vaccines, and these vaccines will elicit an immune response when the food is eaten."

He explained when mice were given the oral vaccine, the mice produced antibodies that inactivated diarrhea-causing bacterial toxins.

Cost is a major factor: The highly effective new vaccines being produced today using genetic engineering techniques cost between $50 and $100 for each dose, while this new mechanism -- the banana -- could cost pennies to deliver.

Eight large banana plants grow in the institute's greenhouse on the Cornell campus. With proper fertilization, lighting, temperature and nurturing, the large-leafed, 14-foot-high plants each produce 100 pounds or more of bananas, said Gregory May, assistant research scientist and part of the research team studying the plant genetics. He said that now researchers know the plants will survive the long Ithaca winters, the team has begun to splice the genes into the banana plants.

Over the next 12 to 18 months, the researchers will conduct feeding studies and generate bananas that will produce a protein from the hepatitis B virus, in order for it to be effective as vaccine, said Hugh Mason, the BTI assistant research scientist who is a viral expert.

Elizabeth Richter, Peter Kipp and Stephanie Clendennen are the research team's plant genetics engineers, and Nicole Higgs and Tanya Simkova are the cell biologists in charge of regenerating plant tissue to make the project sustainable.

This research may be help on the farm, as well. Animals as well as humans could benefit from this technology, Arntzen said.

For example, the technology could be used to deliver vaccines to improve animal disease prevention or for feeding agricultural livestock. Currently, livestock is given antibiotics in their water or by other expensive means to combat a variety of diseases.

BTI is the only major private, independent not-for-profit research institute in the United States focused exclusively on plant research. It is affiliated with Cornell University.