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edible transgenic plant vaccines



November 7, 2002
Prof. Joe Cummins
e-mail: jcummins@uwo.ca

“ Edible transgenic plant vaccines”
Transgenic plants are being are being converted into factories for producing biopharmaceuticals on a large scale while critical comments on the threats of subjects to humans and the environment have been limited. Field testing transgenic plant biopharmaceuticals (pharm crops) that are potent at very small doses has been criticized on the basis that the genes for the dangerous drugs will be transferred and the drugs themselves will accumulate in surface and groundwater along with windblown plant debris . In spite of those concerns the heart drug hirudin ( a drug used for treating angina) is being produced from transgenic plants commercially in Canada. There was little or no public input and awareness of the project and homeowners have not been made aware of activity impacting on their immediate environment. Using transgenic plants to produce large amounts of vaccine at relatively little cost has been the main area of emphasis in medical molecular farming. A large number of transgenic plant vaccines are being developed and field tested . Early tests using a hepatitis B vaccine produced in potato were hampered by the low level of antigen produced in the plant and the safety requirement that only individual previously immunized with injected vaccine be exposed to the plant vaccine for safety concerns . The main safety concern is that the oral vaccine preparations will induce “immune tolerance” making the individual sensitive to the hepatitis B virus. Oral tolerance is a fundamental biological response to ingested antigens making it possible to eat proteins that activate an immune response on injection. The problems associated with the hepatitis B tests seems to have cooled the interests of clinical investigators and pharmaceutical companies .Earlier a vaccine for pig gastroenteritis produced in transgenic corn was claimed to be effective and ready for commercial release by 2003 . Most transgenic plants have been produced using fertile plants and using crop isolation to limit pollen escape. Researchers have employed chloroplast transgene insertions to increase production of the vaccine antigen and to limit the escape of modified genes in pollen (chloroplasts are not transmitted in pollen but are inherited through the mother). However, the chloroplast transgene containment is not proven to be completely effective . The two main concerns over transgenic vaccines are the environmental release of genes in pollen to create crop pollution and of the vaccine itself in plant debris spread as dust and pollution of surface and groundwater with the vaccine. The vaccine antigen may escape to effect browsing animals and humans living in the area of vaccine production who may drink vaccine polluted water or breathe vaccine polluted dust. Earlier, the problem of oral tolerance was pointed out. There is another kind off immune tolerance based on the fundamental concept of self as the immune system is established. Burnet and Medawar found that the immune system established the difference between self and non-self molecules in the developing embryo . Exposing the embryo to vaccine will cause the newborn to be tolerant to the vaccine antigen and thus to regard that antigen as self and the infecting pathogen as self. If the vaccine is polluting the environment individuals born in the area of the pollution will not be able to produce antibodies to the vaccine antigen. A number of transgenic plant vaccines are currently being developed, a number of them will be discussed as follows. Cholera toxin gene was introduced into the chloroplast genome of the tobacco, the construction was geared to high level antigen production to overcome a common problem associated with transgenic plant vaccines, antigen levels too low to elicit immune response, the chloroplast construction allowed 410 times higher antigen production than nuclear gene inserts . Edible cholera B vaccines were produced in transgenic tomato . An antigen gene from the malaria parasite in transgenic tobacco has been proposed to be a malaria vaccine . Mice fed transgenic alfalfa with a gene for an antigen to foot and mouse virus were found to induce antibodies against the foot and mouth virus . That study bears careful scrutiny because alfalfa pollen is known to spread to adjacent crops and pregnant cows and sheep fed on the vaccine crop may bear off-springs tolerant to the virus. Transgenic tobacco was modified to produce vaccines against hepatitis BV and cytomegalovirus, virus like particles were produced and concentrated in the tobacco seeds , however, the modified seeds did not provoke an immune response to hepatitis B and cytomegalovirus in mouse but a strong response to tobacco seed proteins was observed . This experiment shows that the genetic engineering is not always predictable. A transgenic potato was loaded with genes for cholera, E.coli fimbrial antigens and rotavirus entero toxin and adult mice were found to produce antibodies to the toxins after feeding on the transgenic potatoes, neonate mice passively immunized by suckling mice fed transgenic potatoes had less diarrhea than neonates unexposed to vaccine . The transgenic crops produced may be beneficial ultimately but the human and environmental consequences of their cultivation needs fuller study. It is imperative that the cultivation and production of pharm crops , particularly those producing vaccines, be limited to controlled production facilities such as greenhouses that prevent environmental release of the biopharmaceuticals.

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