Therapeutic Vaccines for Allergy in GM Rice

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Therapeutic Vaccines for Allergy in GM Rice

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Fri, 31 Mar 2006 14:04:01 +0100

 

 

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This article can be found on the I-SIS website at

http://www.i-sis.org.uk/TVTFA.php

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ISIS Press Release 31/03/06

 

Therapeutic Vaccines for Allergy in GM Rice

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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

[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.

 

 

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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 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 [6].

 

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.

 

References

 

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, S69-S76.

 

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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