| Making vaccines
from plants |
14th June 1998
"A BIO Symposium on Medicine in the 21st Century" Bio '98 - International
Biotechnology Exhibition
New York, USA - 14th/18th June 1998
"Tasty Vaccines - Genetically Engineered Fruits and Vegetables"
by Dr Iain Cubitt, Monday 15th June 1998
Speaking at the Bio '98 Symposium in New York today, Dr Iain Cubitt of Axis Genetics plc outlined the rapid progress being made around the world in the race
to develop safe new vaccines from plants. These can be either eaten, based upon edible
plants or taken nasally based on purified plant virus particles to stimulate mucosal
tissues which make up 75% of the bodies immune system, hence their immediate and long-term
effectiveness. Injected vaccines target systemically.
The pioneering work now being undertaken in the UK by Axis Genetics has provided a unique
bridgehead for academic institutions around the world interested in their patented CVP
technology. Using this EPICOAT® technique it is now possible to modify plant viruses so
that they effectively become living vaccine factories presenting biologically active
polypeptides on their
surface which can then be harvested.
The plant kingdom's ability to provide effective drugs for medical use has been know for
many years. It is only recently though that plants have come to be regarded from an
equally valuable but unusual point of view, that of production plant for human and animal
vaccines.
Dr Iain Cubitt showed delegates at the Symposium that producing vaccines from plants was
now a practical and commercial reality. By perfecting a way to modify plant viruses and
direct genetic
modification of edible plants to stimulate the body's immune system the company has paved
the way for vaccine production to be transferred from factory to greenhouse within the
next decade.
The new generation of vaccines initially produced in this way would target largely
intractable diseases as a first priority.
Travellers diarrhoea for example is an early target for edible vaccines. A recent Phase I
clinical trial entailed giving volunteers three doses of between 50g and 100g of raw
peeled potato
containing the new vaccine to eat over a three week period. A four-fold rise in both serum
and intestinal antibodies, both of which are likely to protect against the virulent E.
coli enterotoxin
virus, was shown.(1)
Dr Cubitt also reviewed progress on the world's first edible vaccine to protect against
Norwalk virus, a major cause of water and foodborne gastroenteritis not attributable to
bacterial
pathogens. The capsid protein which protects against this illness can only be
obtained from insect cells and plants. Current work on an oral vaccine is progressing well
and the immune system of mice, orally immunised by eating potato tubers containing
recombinant Norwalk virus-like particles, stimulated the production of antibodies against
the capsid protein (2). The Boyce Thompson Institute in America is working with the Baylor
College of Medicine in Houston on this project.
Work is now underway on the production of a new edible hepatitis B vaccine. The high cost
and poor compliance with booster doses are currently major limitations with conventional
vaccines. Boyce Thompson are working to produce the HBsAg (needed to provide the
protection, conventionally produced in yeast, purified and injected) in tobacco and potato
plants and results produced by Roswell Park Cancer Institute in Buffalo show that the
antibody response of mice immunised with the edible plant vaccine is generating the
specific antibodies needed for protection (3).
Other fast track targets currently in progress include the work on cholera by Loma Linda
University in America (4). Rabies protection may also soon be possible and tomatoes and
spinach are both producing the necessary G protein in current experiments (5). This is
work being undertaken by the Thomas Jefferson University. The Flinders University of South
Australia is also working to develop a new oral measles vaccine. The H protein needed is
being produced in tobacco plants.
References
1. Carol O. Tacket, Hugh S. Mason, Genevieve Losonsky, John
D. Clements, Myron M. Levine & Charles J. Arntzen.
Immunogenicity in humans of a recombinant bacterial antigen
delivered in a transgenic potato. Nature Medicine. 4 (5), 607-609,
May 1998.
2. Hugh S. Mason, Judith M. Ball, Jian-Jian Shi, Xi Jiang, Mary
K. Estes & Charles J. Arntzen. Expression of Norwalk virus
capsid protein in transgenic tobacco and potato and its oral
immunogenicity in mice. Proc.Natl.Acad.Sci USA. 93, 5335-5340,
May 1996.
3. Yasmin Thanavala. Novel approaches to vaccine development
against HBV. Journal of Biotechnology. 44, 67-73, 1996.
4. Takeshi Arakawa, Daniel K.X. Cjong & William H.R.
Langridge. Efficacy of a food plant-based oral cholera toxin B
subunit vaccine. Nature Biotechnology. 16, 292-297, March 1998.
5. Peter B. McGarvey, John Hammond, Margaret M. Dienelt, D.
Craig Hooper, Zhen Fang Fu, Bernhard Dietzechoid, Hilary
Koprowski & Frank H. Michaela. Expression of the rabies virus
Glycoprotein in transgenic tomatoes. Biotechnology. 13
1484-1487, December 1995.
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