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[SANET-MG] vaccine for allergy in rice crops
ISIS Press Release 31/03/06
Therapeutic Vaccines for Allergy in GM Rice
Known to cause asthma in clinical trials. Prof. Joe Cummins
The immune system has learned to distinguish between self and non-self.
The cells lining the digestive system or airways encounter antigens in
food and numerous non-pathogenic bacteria. To cope with food or bacteria
that are not harmful, the immune system develops oral tolerance.
Repeated exposure to antigens in food or harmless bacteria leads to a
state of oral tolerance in which the antigen is recognized as self and
does not provoke an immune response .
Allergic and autoimmune diseases are forms of immune hypersensitivity
that increasingly cause ill health. Most current therapies for the
diseases treat symptoms rather then the underlying causes. The
pathologically hypersensitive can be desensitized using vaccines
consisting of synthetic peptides representing ‘T cell epitopes’, the
portion of the antigens provoking the immune response . T cells are
the key mediators of specific immune responses against infectious
diseases or cancer, and are also involved in allergies. A crucial event
in T cell activation is the presentation of peptides derived from
protein antigens. This event is accomplished by the intracellular
fragmentation of specific protein antigens, followed by the binding of
the resultant peptide epitopes to HLA (Human Leukocyte Antigen)
molecules and presented on the cell surface of antigen presenting cells
(APCs) for recognition by specific T-cell receptors.
Synthetic T-cell epitopes derived from the primary sequence of allergen
molecules are used to down regulate allergic inflammation in sensitized
individuals in a manner similar to oral tolerance. The approach has a
substantial advantage over treatment with entire allergen molecules,
which often persist in activating the cells involved in allergic
inflammation . The therapeutic peptide epitopes are ingested,
delivered through airways or injected into the bloodstream. Clinical
trials of T cell epitope peptides using injection proved equivocal; a
number of studies found that the peptides actually induced an asthmatic
GM rice was developed to treat allergy. This development may lead to an
avalanche of GM pharm crops to fight allergies such as cat, dust mites,
nuts, etc. The T cell epitopes for the Japanese cedar pollen allergy
peptide are used to create oral tolerance (oral intake of allergens to
create tolerance by causing the immune system to regard the allergen as
food and thus safe). The epitope peptides are selected, cutting out the
parts of the original protein triggering the allergy response, sneezing,
coughing , etc). Inducing oral tolerance relieves the allergic response
to cedar pollen. Introducing the T- cell epitopes into rice is achieved
by introducing the gene segment specifying the epitope causing the
allergy in humans fused to the soybean seed storage protein glycinin
into the rice genome so that a rice meal should prevent the allergic
response to cedar pollen. The epitope gene was driven by a rice glutelin
promoter, followed by a glutelin signal peptide sequence, a rice
endoplasmic retention signal and a transcription termination gene from
rice glutelin. The gene insert cassette also included a hygromycin
antibiotic resistance gene driven by a CaMV promoter and transcription
was terminated by a agropine sequence [5, 6]. Sneezing transgenic mice
exposed to the allergen were relieved of allergy symptoms and the
accompanying serum allergen IgE and IgG antibodies and CD4+
proliferation response .
The use of rice to treat allergy has the potential to pollute the rice
food crop with genes causing allergy in humans and an antibiotic
resistance gene. The report also did not consider detrimental
side-effects of the epitope peptides, for example the asthma reported in
humans during clinical trials. However, there is little doubt that the
use of human T cell epitope peptides produced in crop plants to treat a
wide array of allergies and autoimmune diseases is going to be a major
focus in the very near future. These developments may well exacerbate
the current “major epidemic” of asthma if unchecked.
Please send this paper to your policy-makers and demand strict
regulation, risk assessment and safety studies on these crops.
Mayer L. and Shao L. Therapeutic potential of oral tolerance. Nature
Rev. Immunol. 2004, 4, 407-19.
Larche M. and Wraith D. Peptide-based therapeutic vaccines for
allergenic and autoimmune diseases. Nature Medicine supplement 2005, 11,
Verhoef A, Alexander C, Kay A. and Larche M. T cell immunotherapy
induces a CD4 T cell population with regulatory activity. PLOS Medicine
2005, 2, 0253-0261.
Linhart B. and Valenta R. Molecular design of allergy vaccines. 2005,
current opinion in immunology 17,1-10.
Takagi H, Saito S, Yang L, Nagasaka S, Nishizawa N and Takaiwa F. Oral
immunotherapy against a pollen allergy using a seed based peptide
vaccine. Plant Biotechnology Journal 2005, 3, 521-33.
Takagi H, Hiroi T, Yang L, Tada Y, Yuki Y, Takamura K, Ishimitsu R,
Kawauchi H, Kiyono H, and Takaiwa F. 2005 A rice-based edible vaccine
expressing multiple T cell epitopes induces oral tolerance for
inhibition of Th2-mediated IgE responses.. Proc. Natl Acad. Sci. USA.
2005 doi/10.1073/pnas.0503428102 (early edition Nov. 8)
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