Risks of Edible Transgenic Vaccines
By Prof. Joe Cummins, Isis.org
Early tests of a hepatitis B vaccine in potato were hampered by the low levels of antigen produced in the plant, and by the safety requirement that only individuals previously immunized with injected vaccine should be exposed to the plant vaccine. The main safety concern is that the oral vaccine preparations will induce “immune tolerance”, thereby making the individual susceptible to the hepatitis B virus.
Oral tolerance is a fundamental biological response to ingested antigens, so that it is possible to eat proteins that would produce an immune response if injected. These difficulties appear to have cooled the fervour of clinical investigators and pharmaceutical companies. Though earlier, a vaccine for pig gastroenteritis produced in transgenic corn was claimed to be effective and ready for commercial release by 2003.
The two main concerns over transgenic vaccines are the contamination of food crops through cross pollination and of the vaccine itself in plant debris spreading as dust and as pollutants in surface and groundwater. The vaccine antigen may affect browsing animals and humans living in the area drinking vaccine-polluted water or breathing vaccine-polluted dust. The problem of inducing oral tolerance has already been pointed out above.
There is another kind of immune tolerance that could be acquired during embryogenesis. 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 and thus to regard both the vaccine and the infecting pathogen as ‘self’. Individuals born in the vaccine-polluted area may well not be able to produce antibodies to the vaccine antigen, and thus to lack protection against infection by the pathogen.
A number of transgenic plant vaccines currently being developed will be discussed. Cholera toxin gene was introduced into the chloroplast genome of the tobacco, the construction was geared towards high levels of vaccine-antigen production The chloroplast construction allowed 410 times higher antigen production than nuclear gene inserts.
Edible cholera B vaccines were produced in transgenic tomato. And an antigen gene from the malaria parasite in transgenic tobacco has been proposed as a malaria vaccine.
Mice fed transgenic alfalfa with a gene for an antigen to foot and mouse virus were found to produce 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 give birth to offspring tolerant to the virus.
Transgenic tobacco was modified to produce vaccines against hepatitis B virus 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. Instead, a strong response to tobacco seed proteins was observed. This unexpected result ought to serve as warning of the unpredictable risks inherent to the transgenic process.
A transgenic potato was loaded with genes for cholera, E.coli antigens and rotavirus enterotoxin, and adult mice were found to produce antibodies to the toxins after feeding on the transgenic potatoes.
The alfalfa mosaic virus was used to produce rabies vaccine in spinach and tobacco. The experiments progressed to having people eat spinach leaves (salad) containing the vaccine. Such vaccines with recombinant viral vectors should have been handled with very great care to prevent the viral vector from recombining and spreading to infect crops in the field.
The rabies vaccination may be important for wild animals and humans, but problems associated with oral tolerance or exposure of children in the womb should be addressed before these vaccines are released to the environment, as the release could actually increase the spread of rabies.