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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.
.