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[SANET-MG] vaccines for allergy in rice
Therapeutic Vaccines for Allergy in GM Rice
Prof. Joe Cummins
A Chinese proverb goes: “If you are planning for one year, grow rice;
for 20 years, grow people; for centuries, grow trees.”
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 [1].
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 [2]. 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 [3]. 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
response [4].
GM rice was developed to treat allergy. This development may lead to an
avalanche of GM pharm crops humanized 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(this is confusing. The epitope
usually means that part of the antigen eliciting the immune response, or
have I missed something?you are absolutely right!) 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).GM sneezing mice exposed to the allergen were relieved of allergy
symptoms and serum allergen IgE and IgG antibodies and CD4+
proliferation response (6).
The use of rice to treat allergy has a potential ability to pollute the
rice food crop with genes causing allergy in humans and an antibiotic
resistance gene. The report did not consider detrimental side effects of
the epitope peptide , for example the resultant asthma reported in
humans 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. It is important to insure that these pharmaceutical
crops are adequately tested for safety to humans and to the environment
before they widely pollute the environment and food supply.
References
1.Mayer,L. and Shao.L. Therapeutic potential of oral tolerance Nature
Rev. Immunol. 2004,4,407-19
2. Larche,M. and Wraith.D. Peptide-based therapeutic vaccines for
allergenic and autoimmune diseases Nature Medicine supplement 2005
,11,S69-S76
3. 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
4. Linhart,B. and Valenta,R. Molecualr design of allergy vaccines 2005,
current opinion in immunology 17,1-10
5. 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
6. 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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