By Katharina Schoebi, Checkbiotech

An oral vaccination against pathogens causing intestinal diseases would offer many advantages. However, until now, the digestion proteins in the stomach has hindered a successful immunization. Now, plant-derived vaccines should offer a new strategy for the prevention of diarrheal diseases.

Carol Tacket from the Center for Vaccine Development at the University of Maryland School of Medicine in Baltimore, USA, has written a review in the journal Vaccine about plant-derived vaccines against diarrheal diseases*.

Vaccines are made of specific antigens from viral, bacterial, and parasitic pathogens causing diseases in humans and animals. By introducing these antigens in the blood stream, the immune system is stimulated and begins to fight off the pathogens.

For many years, researchers have tried to investigate oral vaccines for the treatment of diseases caused by pathogens that infect the gastrointestinal tract, such as the enterotoxigenic Escherichia coli (E. coli), a bacterium causing diarrhea, and Vibrio cholerae, the causative organism of cholera. However, until now, the digestion process of the stomach has hindered a successful immunization.

Nowadays, there is new hope that plant-derived vaccines could be used to fight against enteric pathogens, because the plant cell wall would potentially protect the antigen in the stomach and intestine.

Plants as production systems for vaccines

To manufacture plant produced antigens, biologists introduce the genes of interest into plantlets, which are then able to produce a stable antigen. By eating the genetically engineered plants, the antigen induces an immune response, which leads to successful vaccination– there is no more need for needles and syringes.

Furthermore, transgenic plant vaccines have a variety of other significant advantages over other vaccine strategies. Plants are relatively easily manufactured, packaged, stored and transported. And by using plant-derived vaccines, there is no concern about an infection from human and animal pathogens. A great advantage, especially for the developing world, is that genetically modified plants can be grown locally in an area that needs vaccination.

Potatoes and corn against diarrhea

Some prototypical vaccines against intestinal pathogens, such as E. coli and cholera, have already been developed. E. coli is toxic because it contains a highly immunogenic enterotoxin. Antibodies directed against this toxin could hinder it to bind to the surface of the intestinal cells, and by so doing protect the body against diarrhea. Researchers have genetically engineered potatoes, so that they produced a subunit of this enterotoxin. All volunteers eating these potatoes showed a response of the intestinal immune system, and 73% of them developed antibodies neutralizing the toxin. This indicated the potato vaccine elicited a response that produced fully functional antibodies.

Another scientist developed a genetically engineered corn producing the toxin-subunits of E. coli. Corn is inexpensive to grow and can be scaled up rapidly. Furthermore, corn-derived proteins can be produced at high levels, up to 10 milligram per gram of corn germ, whereas they are very similar to native source protein. Furthermore, they are stable and can be highly concentrated in the corn germ. The corn-derived antigens also stimulated the immune system of the volunteers, who have eaten the genetically engineered corn.

No chance for cholera by eating potatoes

Potatoes have also been used as a vaccine against the bacterial pathogen Vibrio cholera. This organism causes watery diarrhea and vomiting in patients: up to 20 litre of fluid can be lost in just one day. V. cholera also produces a toxin and by integrating a subunit of this toxin in potatoes, the transgenic potatoes were able to stimulate an immune response. In mice, there was a 60% decrease in fluid loss compared to mice that were fed non genetically engineered potatoes.

Concerns about an allergy-induction

However, there are also concerns about the safety of genetically engineered plants acting as vaccine strategies. For example, oral tolerance to the antigen could be stimulated by repeatedly eating the plant-vaccines. This could lead to a poor immune response, if the vaccinated people were confronted with that same antigen in the future during natural infection.

However, preliminary studies in humans have demonstrated, that repeated ingestion of oral antigen actually induced an immune response. The currently licensed oral vaccines are quite safe, and this helps reassure that orally delivered antigens do not induce tolerance to vaccine antigens.

* Plant-derived vaccines against diarrheal diseases, Tacket, C., Vaccine, 23 (2005), 1866-1869

Katharina Schoebi is a Science Writer for Checkbiotech.