SCIENCE

Edible Vaccine to Revolutionize Medicine

Around the world, millions of people are infected every year with pathogenic bacteria such as Vibrio cholerae and enterotoxigenic E. coli. Help may soon be at hand for those most vulnerable, however, as Professor Hiroshi Kiyono and his group at the University of Tokyo have succeeded in developing the first rice-based cholera oral vaccine. Takashi Sasaki reports.

The majority of pathogens, which cause everything from last year’s widespread flu, to cholera, tuberculosis and AIDS, penetrate the human body through the mucosa of the digestive, respiratory and reproductive systems.

Professor Hiroshi Kiyono, who is conducting research on the characterization of the mucosal immune system at the University of Tokyo’s Institute of Medical Science, says, “Until now, all the injected vaccines that have been used to prevent infection were made from detoxified or weakened pathogens that were no longer virulent. By injecting this into the bloodstream, the whole body develops pathogen-specific immunity, forming the defense against infection. If you look at it in terms of preventing an intrusion into a home, it’s like having the police inside your home, but leaving the front door and windows unlocked. On the other hand, with the oral vaccine that we are developing, when it is taken as rice, in powder, tablet or capsule form, the vaccine acts directly on the intestinal mucosa, a part of the digestive system where pathogens enter the body. You could say that it securely locks the doors, preventing a thief from even entering.”


Professor Kiyono’s group is currently working on developing an oral vaccine made by inserting a portion of the cholera bacteria-originated vaccine antigen gene into rice. The vaccine is then cultivated as rice and administered orally in powder form either as is, or in tablet or capsule form, without the use of a delivery device such as a needle and syringe.

“The part of the body that requires immunity to the cholera bacteria is the mucosa of the intestinal digestive tract. The most important point is how stable a form of the vaccine can be delivered to that area. The problem is that before it can reach the mucosal immune system associated with the intestine, the vaccine is usually digested or broken down. Rice is the ideal vaccine delivery vehicle for the digestive tract, since it has a unique and stable protein storage system which can tolerate digestive enzymes in the intestine. And what is more, the antibodies that are made in the mucosa eventually spread to the whole body, so ‘besides the doors being securely locked, the police are inside the home,’ creating an impregnable crime prevention system within the body,” says Professor Kiyono.

In 2010, when powder made from the rice expressing the vaccine antigen cultivated in the laboratory was orally given to mice, antibodies were produced in their intestinal tract mucosa that blocked penetration of the toxin produced by cholera bacteria, and a curbing of the effectiveness of cholera bacteria-induced diarrhea was confirmed.

As well as rendering the administration of vaccine by injection unnecessary, another benefit of rice-based oral vaccines is that they can be stored for long periods at room temperature, without the refrigeration which is generally required for most of the current injection-type vaccines, Professor Kiyono points out. The effectiveness of rice-based oral vaccine has been verified to remain unchanged even after being stored at room temperature for three years, which gives it an overwhelming advantage since it makes storage and shipping easy. Also, since oral vaccines can be administered as is, they not only help conserve resources, but also prevent secondary infection by other pathogens, which often happens when disposable type needles and syringes are reused. One potential of rice-based oral vaccines with these characteristics is that they could bring about groundbreaking change to medical treatment in developing countries, where infrastructure is poor.


In the 1990s, mainly in Europe and the United States, development began of oral vaccines that use plants such as wheat, bananas and tobacco leaves, but they have not yet been put into practical use. The fact that Professor Kiyono’s research group, which started in 2003, was able to quickly work towards the goal of clinical testing, could be said to be due to their focus on rice. Research into the DNA of the Japanese staple food started early and was completed in 2002. Through this research, it was clear which parts of the DNA performed which functions. Professor Kiyono says that the work of Japan-based plant biologists with their expertise in the field of agriculture science was beneficial in ascertaining which genes could be changed to make rice act as a vaccine. This cross-fertilization of the two distinct fields of medical and agriculture science led to the creation of the new concept of “rice as a vaccine production, storage and oral delivery system for medicine” out of the traditional concept of “rice as food.”

“To prevent the genetically engineered rice plants from crossbreeding with rice plants in nature, the rice has to be cultivated in a closed environment. But once you’ve set up the most optimal in-house harvesting environment, it can be harvested three times a year. Compared with traditional vaccines, the cost is remarkably low, and large quantities can be produced.”

Since this is an entirely new form of vaccine production and storage system and one that is taken orally, to ensure its safety it will take several more years of further animal testing and clinical testing before it can be made into an actual medical product. This R&D is looked upon with great expectation by medical professionals all over the world.

Furthermore, through rice-based genetic engineering, it might be possible to prevent a wide variety of infectious diseases besides just cholera. Currently, Professor Kiyono’s team is researching uses against other infectious diseases, such as influenza.

Takashi Sasaki is a freelance writer.