WO2022003429A1

WO2022003429A1 - Allergen desensitisation

Info

Publication number: WO2022003429A1
Application number: PCT/IB2021/050809
Authority: WO
Inventors: John SINN
Original assignee: Sinn John
Priority date: 2020-06-30
Filing date: 2021-02-02
Publication date: 2022-01-06
Also published as: AU2021301341A1; AU2023100077A4

Abstract

The present invention provides a composition for stabilising the immune system prior to allergen desensitisation. The composition comprises a probiotic, a polyphenol extract derived from cocao plant and a vitamin D compound. The probiotic is a species of Lactobacillus selected from a group consisting of Lactobacillus rhamnosus. Further, the present invention provides a modified food allergen used in allergen desensitisation. The food allergens are modified by heat treatment to reduce allerginicity of epitopes present in a food allergen. The modified food allergens are administered at stages where the composition comprising probiotic, a polyphenol extract and vitamin D is first administered to an individual for 2 months before starting allergen desensitisation with the modified food allergen.

Description

ALLERGEN DESENSITISATION

FIELD OF INVENTION

The present invention relates to a composition for stabilising the immune system for purposes of allergen desensitisation and a method thereof. In particular, the present invention provides a composition and its use in allergen desensitisation.

BACKGROUND ART

Food allergy commonly affects 5-10% of children and 2-4% of adults in Australia and New Zealand. Statistics indicate that Australia has the highest incidences in the world. Allergies occur as a result of an overreaction of the immune system when presented with an allergen. The allergen although not harmful is identified by the body as harmful in individuals having allergies. First exposure to the allergen will cause the body to develop antibodies and when the same allergen is exposed again later, an allergic reaction occurs. The most common food allergens include peanut, tree nuts, egg, cow’s milk, sesame, wheat, fish and crustaceans and soy. Some of the most common reactions for a patient having allergies are allergic rhinitis, asthma, eczema or in more severe cases swelling around the lips, hives which may lead to airway swelling which can be life threatening.

Allergies may be severe enough to interfere with an individual’s quality of life. Flence, most individuals having allergies will rely on suitable treatments in overcoming the allergies so that it does not adversely affect their daily life activities. The most common form of treatments are allergy drugs, eg corticosteroids and antihistamines, and immunotherapy. Allergy drugs are medications taken to control allergies. Flowever, they do not cure individuals of allergies. Allergen immunotherapy is the closest treatment to a sustained cure for those having allergies.

Allergen immunotherapy also known as allergen desensitisation involves the regular administration of gradually increasing doses of traces of allergen over a period of time. Allergen desensitisation can be administered to an individual as an injection, orally in the form of tablets or in sublingual sprays. Allergen desensitisation causes change in the way the immune system reacts to a particular allergen by shutting off allergy and causing the individual in due time to be immune to the allergen by achieving tolerance. Allergen desensitisation is important as it provides an individual with a sustained or lasting effect against allergens and is considered more effective than relying on medications to suppress allergies. Some common allergen desensitisation methods include focus on sustained unresponsiveness or relying on ongoing exposure to the allergen.

Most studies on allergen desensitisation focuses on ongoing exposure to the allergen itself whether in modified or not modified form without the need to intake a composition to stabilise the immune system.

One example of exposing an individual to the allergen itself is disclosed in United States Patent Publication No. US 2011/0142867 A1 , hereinafter referred to as US 867, entitled “Immunotherapeutic Methods and System” having a filing date of 20 August 2010; Applicant: Larche et al. US 867 relates to a method for desensitising an individual to a polypeptide allergen or auto antigen comprising a T cell epitope. Subsequently a second polypeptide allergen is administered to the individual where the hyporesponsive state which was induced is sufficient in desensitizing an individual to the second polypeptide allergen. The method is based on creating a ‘tolergeneic environment’ where tolerance to a milder allergen is established first that will lead to tolerance to a more serious allergen.

Another example of exposing an individual to the allergen itself is disclosed in Australian Patent No. AU 2012228033 B2, hereinafter referred to as AU 033, entitled “Treatment for peanut allergy’ having a filing date of 16 March 2012, Applicant: Cambridge University Hospitals NHS Foundation Trust. AU 033 discloses a method for desensitisation of patients having peanut allergy by oral immunotherapy with a peanut protein allergen itself. It involves increasing the oral dose of peanut protein in stages for a duration of at least 2 years. The peanut protein allergen is administered alone after checking the tolerance of an individual to peanut allergen by assessing the results of a skin prick test of a patient.

A further example of exposing an individual to the allergen itself is disclosed in Japan Patent Publication No. JP 2008081458, hereinafter referred to as JP 458, entitled “Desensitizing food and desensitizing drug for wheat allergy” having a filing date of 28 September 2006, Applicant: Omu Milk Products Co. Ltd. JP 458 discloses a wheat desensitization food or desensitization drug containing flour that has been reduced in protein by degrading allergens. The method of developing the desensitized food or drug is based on the technique of hydrolysation of protein that leaves a small amount of antigenicity of the protein molecule. Further, degraded allergen containing wheat flour has been subjected to gel filtration HPLC analysis.

There are some disadvantages on relying on methods of ongoing exposure to the allergen itself. Treatment takes a longer period of time. Further, there may be ongoing side effects that are caused by the allergen as an individual is directly exposed to the allergen from the beginning. Besides that, this form of treatment is not recommended for all forms of allergies especially for those with severe allergies that leads to anaphylaxis. On top of that, ongoing tolerance is not guaranteed after desensitisation is complete. Hence, there is a need for more studies on allergen desensitisation pertaining to sustained unresponsiveness in order to achieve ongoing tolerance after desensitisation is complete.

SUMMARY OF INVENTION

One aspect of the present invention provides a composition for stabilising an immune system of an individual for allergen desensitisation, the composition comprising at least one type of probiotic; a polyphenol extract; a vitamin D compound; and a modified food allergen characterised in that the at least one type of probiotic is a species of Lactobacillus selected from a group consisting of Lactobacillus rhamnosus; and the polyphenol extract is derived from a plant.

Another aspect of the present invention provides a composition wherein the polyphenol extract is derived from a cocoa plant.

Yet another aspect of the present invention provides a composition that is orally administered to an individual having a form of food allergy, wherein the daily dose is increased weekly in a series of increment until an equivalent of 3000 fold or more of the whole form of a food allergen is consumed by the individual.

Another aspect of the present invention provides a method of preparing a composition for stabilising an immune system of an individual for allergen desensitisation comprising steps of stabilising Th2 response by intake of at least one type of probiotics and cacao; inducing a Th1 response by intake of the at least one type of probiotics and cacao; and preparing a modified food allergen; characterised in that preparing a modified food allergen comprises steps of: selecting a plurality of similar food allergens of different origins (202); altering allergenicity of the plurality of similar food allergens by heat treatment (204); manufacturing a plurality of capsules/satchet comprising the plurality of similar food allergens that have been altered (206); coding various level of allergenicity of the plurality of capsules or satchet (208, 300); and selecting one of the plurality of capsule or satchet for use in a first trial for allergen desensitisation (210).

Yet another aspect of the present invention provides a method of preparing a composition for stabilising an immune system of an individual for allergen desensitisation wherein coding various level of allergenicity of the plurality of capsules or satchets (208, 300) comprises steps of: categorizing the plurality of capsules or satchet comprising the plurality of similar allergens that have been altered based on an epitope source (302); categorizing the plurality of capsules or satchet comprising the plurality of similar allergens that have been altered based on temperature production from 0°C to 280°C (304); determining the allerginicity of the plurality of capsules or satchet using testing reagents (306); and marking the plurality of capsules or satchets from least allergenic to most allergenic (308) as part of the food allergenicity ladder.

Another aspect of the present invention provides a method of preparing a composition, wherein selecting a plurality of similar food allergens of different origins (202) comprises selecting at least one food allergen comprising a peanut protein.

Yet another aspect of the present invention provides a method of preparing a composition, wherein selecting a plurality of similar food allergens of different origins (202) comprises selecting at least one food allergen comprising a dairy protein.

Another aspect of the present invention provides a use of a composition for the manufacture of a medicament for administering to an individual to induce tolerance of the individual to a food allergen.

Yet another aspect of the present invention provides a use of a composition wherein the composition is administered daily for at least 2 months.

Another aspect of the present invention provides a use of a composition, wherein the composition is used in combination with a modified food allergen, the composition is administered daily for at least 2 months prior to intake of the modified food allergen.

The present invention consists of features and a combination of parts hereinafter fully described and illustrated in the accompanying drawings, it being understood that various changes in the details may be made without departing from the scope of the invention or sacrificing any of the advantages of the present invention. BRIEF DESCRIPTION OF ACCOMPANYING DRAWINGS

To further clarify various aspects of some embodiments of the present invention, a more particular description of the invention will be rendered by references to specific embodiments thereof, which are illustrated in the appended drawings. It is appreciated that these drawings depict only typical embodiments of the invention and are therefore not to be considered limiting of its scope. The invention will be described and explained with additional specificity and detail through the accompanying drawings in which:

Figure 1 .0a is a table illustrating the amount in CFU of probiotics LGG in the composition of the present invention.

Figure 1 .Ob is a table illustrating the amount of cacao in the composition of the present invention.

Figure 1 .Oc is a table illustrating the amount of vitamin D in the composition of the present invention.

Figure 2.0 is a flowchart of a method of preparing a modified food allergen of the present invention.

Figure 3.0 is a flowchart of a method of coding various level of allergenicity of the plurality of capsules or satchets.

Figure 4.0 is a table illustrating food allergens and various food processing method for modifying food allergens.

Figure 5.0 is a flowchart of a method of administering the composition and the oral allergen in allergen desensitisation.

Figure 6.0 is a table illustrating the amount of modified food allergen in a capsule or satchet DETAILED DESCRIPTION OF THE DRAWINGS

The present invention relates to a composition for stabilising the immune system for purposes of allergen desensitisation and a method thereof. In particular, the present invention provides a composition and its use in allergen desensitisation. Hereinafter, this specification will describe the present invention according to the preferred embodiments. It is to be understood that limiting the description to the preferred embodiments of the invention is merely to facilitate discussion of the present invention and it is envisioned without departing from the scope of the appended claims.

Composition

The present invention provides a for stabilising an immune system of an individual for allergen desensitisation, the composition comprising at least one type of probiotic; a polyphenol extract; a vitamin D compound; and a modified food allergen characterised in that the at least one type of probiotic is a species of Lactobacillus selected from a group consisting of Lactobacillus rhamnosus; and the polyphenol extract is derived from a cocoa plant. The probiotics may include other Lactobacillus strains such as Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus salivarius, Bifidobacterium Breve and Bifidobacterium animalis. Intake of this composition creates a stabilised and improved immune system before commencing allergen desensitisation. The combination of the components present in the composition is effective in creating an improved immune system prior to desensitisation. Probiotics LGG is said to be beneficial to the gut and improves the digestive system’s ability to tolerate allergens. Cacao polyphenol is important in inducing microbiota growth. It also inhibits Clostridium histolyticum and promotes growth of Lactobacillus and Bifidobacteria species. Vitamin D is important in the proper functioning of T-cells and is pivotal in improving the immune system.

Reference is made to Figure 1 .0a on a table illustrating the amount of Probiotics LGG in the composition. Probiotics LGG of 10 billion colony forming units, CFU is administered to individuals having less than 30 kg of body weight whereas probiotics of 20 billion CFU is administered to individuals having more than 30 kg of body weight.

Reference is now made to Figure 1.0b on a table illustrating the amount of cacao polyphenol in the composition Cacao polyphenol is a vital ingredient in the composition that is extracted from cacao. Cacao contains an active ingredient which is from the flavonoid family with monomer epicatechin, catechin and polymeric forms polyphenols such as Procyanidins. Cacao can modulate TNF alpha and induce NF kappa B which is the transcription to cytokines such as IL1 , IL 2, IL 6, IL 8 and TNF alpha. It can decrease Th2 response and inhibits IL2 gene expression.

Cacao powder has flavanol content of 510 mg/100 g of cacao powder. Different groups of flavanoids are epicatechin, procyanidin, catechin and procyanidin. The amount of epicatechin is 158mg/100g, procyanidin B1 is 112mg/100g, catechin is 107mg/100g and procyanidin B2 is 240mg/100g.

The content of cacao in the composition varies according to an individual of different mass. The measurement of 1 cacao nip is 0.55g/day and 13 g of cacao contains 66 mg of flavanols.

Baby having a weight of approximately 10 kg intakes 5 nips equivalent to 2.75g/day Child having a weight of approximately >20 kg intakes 10 nips equivalent to 5.5g/day Adult intakes is 15-20 nips equivalent to 8-11 g/per day equivalent to 990-1320mg of flavanols per day.

These amounts of cacao in the composition will induce an intestinal tolerogenic pathway mediated dendritic cells to T regulatory cell activation and anti-inflammatory cytokine IL 10.

Reference is made to Figure 1.0c on a table illustrating the amount of vitamin D in the composition. The amount of Vitamin D in the composition is measured at 500IU or 12.5mcg per day.

The method begins by administering an individual with a composition containing cacao polyphenol, probitoics LGG and vitamin D. In the meantime oral allergens are modified where the epitopes are manufactured by timed heat process from raw allergens, boiling to roasting. A skin prick test is performed on a batch of allergen of different epitopes. If the wheal size is < 5mm, allergen desensitisation can be undertaken without a high risk of anaphylaxis. Finally exposure of the allergen is undertaken where increasing doses of the allergen comprising different epitopes are taken until an equivalent to three doses of the food allergen. Allergen desensitisation-modified food allergen

The present invention also includes an improved method of allergen desensitisation. Allergen desensitisation of an individual is initiated by a modified form of allergen. The oral food allergen is modified using protein modification techniques by food processing with heat or hydrolysation that causes modification of the epitope of an allergen. Determining an allergen having an epitope that an individual has minimum reaction would mean successful desensitisation.

Epitopes on food allergens have been coded to be standardized around the world. With reference to journal paper ‘How different parts of the world provide new insight into food allergy, Tham Allergy asthma Immunol Res 2018 July, 10(4): 290-299 individuals from different parts of the world have more allergies to one part of the protein compared to others which is determined by the standardized coding of food allergens. Examples on how allergy affects individuals of different countries are described.

Example 1.1 Peanuts

Individuals from Spain, United States of America and Sweden that have peanut allergies are recorded to be sensitised to Ara h 1 , 2 and 3 which codes for seed storage protein. Individuals from Spain are recorded to be sensitised to lipid transfer protein, LTP coding for Ara h 9. Individuals from Sweden are recorded to be sensitised to homologue Birch pollen the protein Beta V 1 .

Example 1.2 Hazelnut

Individuals having hazelnut allergies cross reacts to birch pollen coding for Cor a 1 in Central and North Eastern Europe and food allergen coding for Cor a 8 in Mediterranean and has cross reactivity to Walnut, peach, apple and tree pollen. An individual that is sensitised to food allergens coding for Cor a 9, Cor a 11 and Cor a 14 will in likelihood be sensitised to nuts, seeds and legumes.

Some examples of food allergens used in the present invention are nuts, egg white, cow milk, wheat. However, the food allergens that are modified are not limited to nuts, egg white, cow milk and wheat and may include any food allergens. Example 2.1 Allergen: Egg white.

Method of modifying epitope on allergen: baking, boiling, scrambled and raw. Timing of heating changes the allergenicity.

Example 2.2 Allergen: Cow milk.

Method of modifying epitope on allergen: hydrolysation; partial hydrolysed, baking, Ultra High Temperature, UHT, pressure cooking, treatment and pasteurisation.

Example 2.3

Allergen: Shrimp: Tropomyosins is heat stable and difficult to modify the allergenicity of the allergen.

Reference is made to ‘Masakatsu Usui Relationship between the risk for a shrimp allergy and freshness or cooking Food & Nutrition Science p 1689-1701 Mar 2015’

Example 2.4 Allergen: Peanut

Method of modifying epitope on allergen: boiling, roasting

In describing further on one of the most common allergy, peanut allergy, it is recorded that peanut allergen codes for Ara h 1-13, Ara h 5 that relates to birch pollen profiling, Ara h 9 that relates to peach allergy, 7S Globulin coding for Ara h 1 that relates to low sensitivity to heat and digestion with pepsin, 11 S Globulin coding for Ara h 3 and 2S albumin coding for Ara h 2 that is resistant to boiling and proteolytic digestion. A peanut allergen comprises 12 allergen isoforms. The peanut allergen comprises proteins that have IgE binding prevalence and significant cross reactivity. There are different IgE epitopes inducing different reactivity to each antigen coding. These proteins are Cupin that codes for Ara h 1 and Ara h 3, Prolamin that codes for Ara h 2, Ara h 6, Ara h 7 and Ara h 9, Profilin that codes for Ara h 5, Beta V 1 that codes for Ara h 8 and Oleosin that codes for Ara h 10 and Ara h 11. These epitopes that have different codings interrelate to each other and account for determining the optimum allergen to be used in allergen desensitisation. It is recorded that certain peanuts depending on its source have no Ara h 3 and these peanuts are recognised as less allergenic. Cross reactivity heavily occurs between codings of Ara h 1 and Ara h 3. Ara h 6 shares 59% to Ara h 2 which is considered the most potent allergen. The minor allergens code for Ara h 5 and Ara h 8. Ara h 8 is a flavanoid carrier protein that binds with epicantechin of cacoa of the present invention for use in allergy desensitisation. A more severe allergic response is based on sensitisation to more than one protein coding different epitopes. An individual having an allergy reaction is when the immune system of an individual recognises one epitope but due to cross reactivity, the individual will be allergic to other major or minor allergens.

Through methods of boiling and roasting, protein allergen such as peanuts denature and undergo glycosylation or glycation which causes the Maillard reaction causing structural and chemical changes that influence allerginicity of the food allergen and in their ability to bind to IgE antibodies. Boiling decreases Ara hi and Ara h 2 and Ara h 6. Hence patients whose IgE to Ara hi , Ara h2 and Ara h6 are high may be able to tolerate boiled peanuts more readily. Roasting increases Ara hi and Ara h2 IgE binding. Glycosylation process causes cross reaction with cross reactive carbohydrate determinants, CCD. Glycosylation state with CCD promotes Th2 response to more allergenicity. In glycation by inducing Maillard reaction, formation of advance glycaemic end products, AGE with sugars react with free amines such as lysine and undergo an Amadori rearrangement. This occurs with high temperature dry roasting and formation of AGE. The formation of AGE modifies Ara h 1 and Ara h 3 which causes indigestion and increase in sensitisation towards Th2 response. This is based on stimulation of the receptor for AGE and activates the IL 4 and 5 producing T cell down the Th2 response and proinflammation. Dry roasting for 15 minutes causes a maximum amount of Ara h 1 compared to shorter roasting time whereas boiling reduces AGE.

Reference is made to Figure 2.0. Figure 2.0 illustrates a method of preparing a composition for stabilising an immune system of an individual for allergen desensitisation. The method comprises steps of stabilising Th2 response by intake of at least one type of probiotics and cacao; inducing a Th1 response by intake of the at least one type of probiotics and cacao; and preparing a modified food allergen (200). The method is further characterised by a method for preparing a modified food allergen (200) for allergen desensitisation comprising steps of selecting a plurality of similar food allergens of different origins (202); altering allergenicity of the plurality of similar food allergens by heat treatment (204); manufacturing a plurality of capsules comprising the plurality of similar food allergens that have been altered (206); coding various level of allergenicity of the plurality of capsules (208, 300); and selecting one of the plurality of capsule for use in a first trial for allergen desensitisation (210). Further, the method of preparing a modified food allergen (200) comprises selecting at least one food allergen (202) comprising a peanut protein.

Reference is further made to Figure 3.0. Figure 3.0 illustrates a method of coding various level of allergenicity of the plurality of capsules or satchets (208, 300). The method comprises steps of categorizing the plurality of capsules or satchets comprising the plurality of similar allergens that have been altered based on an epitope source (302); categorizing the plurality of capsules or satchets comprising the plurality of similar allergens that have been altered based on temperature production from 0°C to 280°C (304); determining the allerginicity of the plurality of capsules or satchets using testing reagents (306); and marking the plurality of capsules or satchet from least allergenic to most allergenic (308).

Altering allergenicity of the plurality of similar food allergens by heat treatment (204) is further described. Altering allergenicity of the food allergens in the present invention is accomplished by heat treatment. Flowever, reducing allerginicity of the food allergens is not limited to heat treatment alone and may include glycation reaction, irradiation, high pressure and enzymatic hydrolysis. Food processing leads to the destruction of epitopes and the forming of new epitopes also known as neoallergens. During food processing, proteins present in the food allergens are denatured, aggregated or involved with Maillard reaction. Some common food processing of the food allergen involving heat includes pasteurisation at 70-80°C for 15-20 minutes, boiling at 100°C in water; ultra high temperature, UFIT processing at 135-145°C for 0.5-4.0 seconds and heating at more than 110°C to induce Mailard reaction for food allergens comprising sugar and protein.

Fleating processes affects different protein differently. For example, autoclaving at 138°C for 15minutes decreases IgE binding. The glycation process that occurs between reducing sugar and free amino acid that causes a Maillard reaction decrease IgG and IgE binding. Blanching relates to leaking protein into the water. Sensitisation is the phase where immunological priming cause an individual’s body to induce Th2 biased immune response and produce IgE antibodies. The key is to decease mast cell degranulation and decrease inflammatory reaction. The composition comprising cacao and probiotics of the present invention decreases the immunological priming that induces IgE antibody response. To divert inducing Th2 biased immune response and IgE antibody response the composition of the present invention is used to promote Th1 response. This is to effect an innate immune response. Modification of food impacts the recognition of APC antigen presenting cell to the antigens.

Pasteurization causes aggregation of B and alpha lactoglobulin that causes binding to APC and Peyer’s patches cause a Th2 response. In describing further on food allergen modification by food processing reference is made to Figure 4.0 on a table illustrating food allergen and various methods of food processing. With regards to cow milk, partial or extensive hydrolysation are used in the first step of desensitisation. If the patient is SPT < 5mm to to a form of hydrolysed version of cow milk protein then they could be use for desensitisation. Next step is baking cow milk protein in muffin which causes Maillard reaction with lactose in milk. The reaction decreases IgG binding capacity of whey protein and Alpha lactalbumin. Maillard reaction also causes conjugation of B lactoglobulin with lactose to decrease IgE recognition. Pasteurisation causes increase in IgE binding as it causes aggregation and activation of mast cells. Another method for food processing is Ultra High Temperature, UHT treatment . Some patients are still allergic to pasteurise milk but are able to tolerate UHT milk. This is usually the last step before the patient is desensitised to pasteurised cow’s milk.

Another food allergen studied is eggs. Heating lowers IgE binding activity in eggs. Baking causes the least IgE response followed by boiling then scramble egg. The longer the heat in scramble egg the less allergenic the protein becomes. Gradual increasing allergenicity is achieved by decreasing time of heat treatment. This will be package in capsule or satchets for the process of desensitisation.

Another food allergen is hazelnut. Hazelnut that is roasted is less allergenic compared to its raw form. This is due to a decrease in IgE binding of the birch pollen related allergen. Hence, blanching and roasting hazelnut compared to its raw form decreases allergenicity.

For the food allergen almond, roasting and blanching is said to be stable in heat. However we have shown boiling decrease allergenicity and able to desensitise patients to Almond using the same technique.

Cashew nut was recorded to have reduced IgE binding capacity and boiling cashews has resulted in desensitisation to Cashews. For brazil nuts that were roasted is said to have no difference in IgE binding. However again, boiling seem to have effect on the allergenicty to Brazil nut protein and able to achieve desensitisation.

With walnuts studies have shown heating to 191°C, blanching, roasting and frying do not effect a difference in IgG binding but the method of autoclaving showed a decrease in epitopes coding jug r 2 and jug r 4. Boiling has also been shown clinically effective in desensitisation.

For pistachios, the method of steam roasting reduced IgE binding. For pecan nuts, roasting and autoclaving is said to decreased IgG binding. Using boiled version of these have also shown clinically to be useful to desensitse.

Peanuts that are boiled exhibited IgE with lower binding compared to its peanut in its raw form. Roasted peanuts in contrast enhanced IgE binding capacity with proteins as it causes increase of AGE. Hydrolysation reduces Ara h 1 and Ara h2 in roasted peanuts. Autoclaving is recorded to decrease IgE binding causing unfolding of basic protein alpha helix and B strand. Frying decreases Ara h 1 and 2 and Ara h 3. As part of the invention, determination of which epitope either by boiling or roasting peanuts with different temperatures needs to be determined individually and confirmation is made by SPT of < 5mm and passing an oral challenge.

For wheat, Lactobacillus used in fermentation produces sour dough can degrades IgE epitopes. This wheat preparation as part of the invention can be used for desensitisation.

Soy is another food allergen that is also associated with birch pollen protein Bet v 1. Like wheat, fermentation of soy decreases IgE binding capacity. Heating that causes Maillard reaction also reduces IgE production. Besides high pressure processing on soy causes non covalent bonds, hydrogen, ionic and hydrophobic bonds to be broken.

For prawns, the method of processing slightly differs. Desensitisation could be achieved by desensitisation to a relative to prawns. In this case house dust mite which also has tropomyosin allergen. Immunotherapy to HDM has been shown to decrease allergy to prawns and also HDM. Cross species desensitisation can be associated with decrease sensitivity. For fish protein, dark muscle part of a fish is used as part of desensitisation which has less IgE labelled epitopes. Heat treatment to induce Mailard reaction causes antigenicity of parvalbumin to decrease by 75%, reference is made to ‘Impact of Maillard reaction conditions on the antigenicity of paralbumin, Oct 2013 Food and agricultural immunology’.

In describing further on coding various level of allergenicity of the plurality of capsules (208, 300) reference is also made to Figure 2.0. The method involves categorizing the plurality of capsules comprising the plurality of similar allergens that have been altered based on an epitope source (302); categorizing the plurality of capsules or satchets comprising the plurality of similar allergens that have been altered based on temperature production from 0°C to 280°C (304); determining the allerginicity of the plurality of capsules or satchet using testing reagents (206); and marking the plurality of capsules or satchets from least allergenic to most allergenic (308).

Allergen Desensitisation whole process

Reference is now made to Figure 5.0. Figure 5.0 is a flowchart showing an overview of a method of administering the composition and the modified food allergen in allergen desensitisation. The method involves administering a composition to an individual for 2 months prior to intake of the modified food allergen (502); modifying a plurality of modified food allergen by heat treatment and manufactured in capsules or satchets (504); categorizing the plurality of the modified food allergen by allergenicity (506); performing a Skin Prick Test on a subject based on the plurality of modified food allergen (508); undertaking oral challenge with the modified food allergen with least allerginicity where wheal size in Skin Prick test is less than 5mm (510) to the next higher allergenic form of the food tested on the patient previously; increasing dose of the modified food allergen weekly until 3000 times the dose (512); performing Skin Prick Test on a subject for the modified food allergen with higher allerginicty (514); and continuing allergen desensitisation testing until subject is immune to at least 5 of the modified food allergen of different allergenicity (516). In the method of allergen desensitisation, the composition is used for the manufacture of a medicament for administering to the individual to induce tolerance of the individual to a food allergen.

In describing on increasing dose of the modified food allergen weekly commencing at 1 mg until 3000mg (512), reference is made to Figure 6.0. Figure 6.0 shows a table illustrating the amount of food allergen in one capsule or satchet. The daily dose is increased weekly in a series of increment until an equivalent of 3000mg of whole form of a food allergen is consumed by the individual.

Hence the present invention provides for an improved method of allergen desensitisation beginning from intake of a composition comprising probiotics LGG, cacao polyphenol and vitamin D and modifying a food allergen that is capsulated or packaged that will be administered to an individual for allergen desensitisation.

Throughout this specification, unless the context requires otherwise, the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated step or element or integer or group of steps or elements or integers, but not the exclusion of any other step or element or integer or group of steps, elements or integers. Thus, in the context of this specification, the term “comprising” is used in an inclusive sense and thus should be understood as meaning “including principally, but not necessarily solely”.

Claims

1. A composition for stabilising an immune system of an individual for allergen desensitisation, the composition comprising at least one type of probiotic; a polyphenol extract; a vitamin D compound; and a modified food allergen characterised in that the at least one type of probiotic is a species of Lactobacillus selected from a group consisting of Lactobacillus rhamnosus; and the polyphenol extract is derived from a plant.

2. The composition of claim 1 , wherein the polyphenol extract is derived from a cocoa plant.

3. The composition of claim 1 is orally administered to an individual having a form of food allergy, wherein the daily dose is increased weekly in a series of increment until an equivalent of 3000 fold or more of the whole form of a food allergen is consumed by the individual.

4. A method for preparing a composition for stabilising an immune system of an individual for allergen desensitisation comprising steps of: stabilising Th2 response by intake of at least one type of probiotics and cacao; inducing a Th1 response by intake of the at least one type of probiotics and cacao; and preparing a modified food allergen; characterised in that preparing a modified food allergen comprises steps of selecting a plurality of similar food allergens of different origins (202); altering allergenicity of the plurality of similar food allergens by heat treatment (204); manufacturing a plurality of capsules or satchets comprising the plurality of similar food allergens that have been altered (206); coding various level of allergenicity of the plurality of capsules or satchets (208, 300); and selecting one of the plurality of capsule for use in a first trial for allergen desensitisation (210).

5. The method of claim 4, wherein coding various level of allergenicity of the plurality of capsules ot satchets (208, 300) comprises steps of: categorizing the plurality of capsules or satchet comprising the plurality of similar allergens that have been altered based on an epitope source (302); categorizing the plurality of capsules or satchets comprising the plurality of similar allergens that have been altered based on temperature production from 0°C to 280°C (304); determining the allerginicity of the plurality of capsules using testing reagents (306); and marking the plurality of capsules or satchets from least allergenic to most allergenic (308) as part of the food allerginicty ladder.

6. The method of of claim 4, wherein selecting a plurality of similar food allergens of different origins (202) comprises selecting at least one food allergen comprising a peanut protein.

7. The method of claim 4, wherein selecting a plurality of similar food allergens of different origins (202) comprises selecting at least one food allergen comprising a dairy protein.

8. Use of a composition according to claim 1 , for the manufacture of a medicament for administering to an individual to induce tolerance of the individual to a food allergen.

9. The use of the composition of claim 8, wherein the composition is administered daily for at least 2 months.

10. The use of the composition of claim 8, wherein the composition is used in combination with a modified food allergen, the composition is administered daily for at least 2 months prior to intake of the modified food allergen.