Potato Vaccine for Hepatitis B: Syringes off the Menu?

John Roach
National Geographic News
February 15, 2005
Scientists have shown that, for hepetitis B vaccine, genetically modified potatoes may be an alternative to the syringe and needle.

The hepatitis B virus (HBV) causes liver failure and liver cancer. Despite the availability of a safe, injectable vaccine, the virus currently infects an estimated 350 million people worldwide and kills about a million people every year.

In recent years scientists have raced to develop oral vaccines with genetically modified plants as a means to overcome the economic and safety limitations of syringe-and-needle vaccination programs, especially in developing countries.

"The whole concept of oral vaccines, versus injections, is a very attractive one. As you can imagine, we are used to taking things by mouth. They are easy, and there are not associated problems with potential contamination due to syringes and needles," said Yasmin Thanavala, an immunologist at the Roswell Park Cancer Institute in Buffalo, New York.

Previously researchers have shown that potatoes can deliver vaccines for intestinal pathogens such as the E. coli and Norwalk viruses, which enter the body via the mouth.

This week in the research journal Proceedings of the National Academy of Sciences, Thanavala and colleagues report on the first human, or clinical, trial for a plant-derived HBV vaccine. HBV is transmitted by blood or sexual fluids.

Clinical Trial

For the clinical trial, the researchers genetically modified potatoes to carry the gene for the hepatitis B surface antigen. An antigen is a foreign substance, usually a protein, that, when absorbed by the body, triggers an immune response.

In the trial of 42 participants previously inoculated with the traditional hepatitis B vaccine, about 60 percent showed signs of boosted immunity after eating bite-size pieces of raw genetically modified spuds.

Charles Arntzen, a pioneer in the development of plant-derived vaccines and a co-author of the paper, said he was pleased at the success of the trial.

"We had seen very good responses in mice, so anticipated that we might get good responses in humans. But mice and humans are very different, so we were delighted," said Arntzen, who works with the Biodesign Institute at Arizona State University in Tempe.

The results were particularly impressive, Thanavala said, since the vaccine lacked an adjuvant. An adjuvant is a substance added to a vaccine to improve the immune response.

Arntzen added that he was pleasantly surprised that the vaccine apparently withstood the stomach's acids and enzymes. This was an indication that the potato tissue surrounding the vaccine was able to protect it as it journeyed through the stomach to the large and small intestine, where specialized cells initiate immune responses.

Carol Tacket is a professor of medicine at the University of Maryland School of Medicine's Center for Vaccine Development in Baltimore. Though not part of the research team, she is interested in novel approaches to vaccination via the body's mucous membranes, such as those that line the mouth and intestines, and has been involved with the field of plant-derived vaccines. "The whole concept is pretty amazing," she said.

"It seems hard to imagine the mucosal immune system in the intestine would be able to pluck out a bit of protein in a sea of foodstuff and process it in a way for an immune response to be generated," she said.

Oral Vaccines

Thanavala and colleagues are now working to match or better the success of the syringe-and-needle hepatitis B vaccine with their potato-derived version. The traditional vaccine has a success rate of about 90 percent. About 10 percent of all people, for reasons not understood, fail to respond.

"What we've shown is proof of principle that a subunit antigen can be delivered orally and can provoke an immune response. That's the first step," Thanavala said. "Now, can we make improvements to better the overall rate of response to make it a true contender of the current licensed vaccine?"

If successful, the researchers envision a plant-derived hepatitis B vaccine that could serve to boost the immune response of previously vaccinated people in countries like the U.S. And for the 60 percent of the world's children who lack the vaccine, a plant-derived version may be the solution, Arntzen said.

But before people get carried away with visions of plates of genetically modified potatoes being passed around clinics, Arntzen cautioned that the field of plant-derived vaccines has matured over the past decade.

"Initially, plant vaccines were perceived in a way that today seems rather naïve: that is, as a kind of vaccine utopia, whereby people in developing countries would be able to eat antigen-producing fruits and vegetables and be passively immunized against one or more infectious disease," Arntzen said.

Concerns about the safety of the genetically modified crops interacting with other foods and the lack of dose control have since moved researchers to focus on food-processing technologies to package measured doses of vaccine.

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