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Vaccinating with Rice

Researchers have engineered rice to serve as a needle-free vaccine for cholera.

A genetically modified strain of rice that expresses a vaccine for cholera has been developed by researchers at the University of Tokyo. Since the rice-based vaccine comes from an edible plant, it’s safe and inexpensive to produce in large quantities and can be orally administered. It serves as an advance to most traditional plant-based oral vaccines because the rice can be stored at room temperature for at least a year and a half, and, once administered, its protein body protects the vaccine from digestive enzymes that would otherwise render it ineffective. Rice also has greater protein content than some of the starch-based edible vaccines currently under experimentation for a variety of infectious diseases.

Transgenic rice plants: Japanese researchers have inserted the genetic material from the cholera bacterium into Kitaake (above) and Hosetsu rice plants to produce MucoRice–a vaccine for cholera, a severe diarrheal disease.

“There are a number of people who are making transgenic corn, wheat, and soybeans, but what is nice about rice is that it is a major food staple for many developing countries,” says David Pascual, a professor of immunology at Montana State University. “The work being done by the Japanese researchers is very important because it brings a mechanism to propagate vaccines in the underserved portions of the world.”

Cholera is a bacterial disease that affects the intestinal tract. It’s caused by the bacterium Vibrio cholerae and is transmitted to humans through contaminated food and water. Cholera is prevalent in African and Latin American countries and parts of Asia, and worldwide the number of cases has risen almost 30 percent since 2004, according to the World Health Organization. If untreated, the disease can be deadly.

The Japanese researchers created the rice-based cholera vaccine by inserting the genetic material from the cholera bacterium into the sequenced genome of the rice plant. The researchers used two types of rice plants to generate the vaccine: Kitaake, which produces normal rice, and Hosetsu, which produces dwarf-type rice. Once the rice plants produced the toxins, they were fed to mice in a powder form suspended in water. The rice-based vaccine produced antibodies throughout the mice’s bodies including their mucosal sites, which are an important first line of defense since infectious diseases typically invade and infect a person at these sites. As a result, the mice became immune to the diarrhea-causing bacterium.

“Our goal is to develop a new generation of environmental- and human-friendly vaccines, which can induce protective immunity in both mucosal and systemic compartments against infectious microorganism,” says Tomonori Nochi, the vaccine’s lead investigator and a postdoctoral fellow in the Department of Microbiology and Immunology at the Institute of Medical Science at the University of Tokyo. The researchers’ report appears in this week’s edition of the Proceedings of the National Academy of Sciences.

Rice is a plant that can be stored at room temperature for a long time, which is very important for the development of the vaccine. It’s estimated that worldwide, it costs $200 to $300 million each year to preserve vaccines at cold temperatures, explains Nochi. “Thus we termed our technology cold-chain-free vaccine. In addition, purification of the vaccine antigen from rice seed is not necessary, also causing a reduction in cost.”

Furthermore, abolishing the painful use of needles and syringes not only cuts costs, but also prevents pathogens from accidentally appearing in the vaccines and then spreading throughout the population, especially in underdeveloped countries where supplies are limited.

The researchers plan to prepare the rice-based vaccine in the form of a capsule or tablet for applications in humans, hence they don’t have plans to deliver the vaccine as a form of steamed rice. The rice-based vaccine is also suitable for prevention of other mucosal infectious diseases, such as influenza and HIV.

“Genetically altering plants for vaccinations is an important area of research, and the work being done by the Japanese researchers is very exciting,” says Carol Tacket, a professor of medicine at the Center for Vaccine Development at the University of Maryland School of Medicine. “Using plants to express vaccines is technically achievable, and the main barrier is identifying protective antigens–in other words, what proteins will protect when used as vaccines. It’s really identifying the right antigen to put in expressions.”

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