Japanese Researchers Use Rice to Develop Cholera Vaccine

A team of Japanese researchers has developed a type of rice that can carry a vaccine for cholera, a step that could one day ease delivery of vaccines in developing countries.

While it's only the latest of several plants being tested as potential means of producing vaccines, the development is potentially important in medically underserved countries that lack refrigeration to store regular vaccines.

But the work is preliminary, having been tested only in mice.

The team, led by Hiroshi Kiyono of the division of mucosal immunology at the University of Tokyo, reports the development of the new vaccine in Tuesday's issue of Proceedings of the National Academy of Sciences.

A major advantage of this approach, they said, it that it causes immune reactions both systemwide in the body and in mucosal tissues such as in the mouth, nose and genital tract.

Standard vaccines delivered by needle do not spur immune responses in the mucosal areas.

That means the new vaccine could have an advantage against pathogens that typically infect these membranes, such as cholera, E. coli, human immunodeficiency virus, influenza virus and the SARS virus.

Attempts to alter plants to produce proteins that induce an immune reaction to various diseases have been under way for years, but none has reached the state where it could be used in humans.

"This has not progressed to the degree that we had hoped it would by this time," said Hugh S. Mason, a researcher at Arizona State University who has worked on several lines of plant vaccine study.

Mason cautioned that getting a good response to orally delivered material can be tricky in the harsh environment of the digestive system.

"We're going to have to work on ways to protect it from degradation of the stomach and then release it lower down in the gut so it can be taken up," he said.

In 1998 he published a paper on modifying potatoes to produce a vaccine for Norwalk virus. But he said in a telephone interview last week that "was a relatively preliminary study."

Most recently, Mason said, he has been working with nicotiana Benthamiana, a relative of tobacco, but which is smaller and has fewer alkaloids than tobacco.

Many researchers are moving away from food plants because of public concern about altered items getting into the food chain, Mason said.

David W. Pascual, a molecular biologist at Montana State University in Bozeman, said the Japanese researchers were able to generate a protective immune response in the mice while avoiding any allergic reaction to the rice itself.

In addition, the transgenic rice can be stored at room temperature and doesn't have the risks of infection from an injection.

Pascual, who was not part of the research team, noted that several other plants have been developed to carry vaccines.

Potatoes and tomatoes have been tested for vaccine against Norwalk virus, he said, potatoes, corn and soybeans against enterotoxin, potatoes for cholera vaccine, and soybeans for E. coli.

One reason for the slow progress in the field has been lack of interest and funding from major pharmaceutical companies, Mason said.

The only plant-based vaccine in use counters Newcastle disease in chickens, and that reached development only after Dow Agroscience became interested, he said.

The Japanese research was funded by several agencies of the Japanese government.

The use of rice engineered to produce a vaccine reaction doesn't mean it's an edible vaccine, Kiyono stressed.

"We do not wish to create the condition that public is thinking of eating steamed rice for vaccination," he said via e-mail.

Instead, the vaccine is delivered in a capsule or pill containing rice powder and should be treated as a drug, not food, he said.

With the first work done in mice, Kiyono said more basic studies are needed and he hopes to test the vaccine in a primate "in the near future."