WO2005027774A2 - Method and apparatus for preventing allergies - Google Patents

Abstract

Apparatus and methods of preventing allergies in vertebrate animals by exposing the animals to allergens contained in common household and farm articles and materials is disclosed.

Description

Method and apparatus for preventing allergies

CROSS REFERENCE TO RELATED APPLICATIONS This application claims priority pursuant to 35 U.S.C. 119(e) to U.S. Provisional Application Number 60/503799 filed 9/17/03 which is hereby incorporated herein by reference in its entirety including incorporated material.

FIELD OF THE INVENTION

The field of the invention is the field of allergy prevention and control.

OBJECTS OF THE INVENTION It is an object of the invention to produce methods, materials, apparatus, and systems for preventing and controlling allergic reactions in mammalian animals before they have exhibited such allergic reactions. It is an object of the invention to produce methods, materials, apparatus, and systems for preventing and controlling allergies using common household and farm articles to deliver antigens.

BACKGROUND OF THE INVENTION Allergic diseases in general and asthma in particular are on the rise in western societies. From 1980 to 1994, the U.S. Center for Disease Control and Prevention reported that asthma rates in the US increased by 75%. The International Study of Asthma and Allergy in Childhood (ISAAC) and the European Community Respiratory Health Survey (ECRHS), looking to adult respiratory disease, have recently confirmed that allergic diseases are mainly found in industrialized communities and are far rarer in rural Russia, China, India and Ethiopia. Allergic diseases are thought to be the result of inflammatory processes characterized by hypersensitive or exaggerated reactions to common allergens or antigens. Other classes of inappropriate inflammatory processes known as autoimmune diseases are also on the rise in western civilization. For example, Crohn's disease, diabetes mellitus type 1, rheumatoid arthritis and systemic lupus erythematosus have all shown significant increases in the last two decades. Current therapies for allergic diseases are limited to symptom relief and at reducing inflammation mediators. In the case of asthma, for example, typical therapy calls for inhaled corticosteroids, anti-leukotrienes, or receptor agonists. There is a clear lack of therapies designed to prevent the development of allergic and auto-immune diseases before the first symptoms of the disease occurs.

DETAILED DESCRIPTION OF THE INVENTION

Several approaches have been proposed for primary prevention of both allergic diseases and autoimmune diseases (before symptoms of the disease occur), which attempt to induce tolerance by administering allergens subcutaneously (as in the case of immunotherapy for hyposensitization) or orally (as in the case of oral tolerance induction). For subcutaneous immunotherapy, Warner et al. (Warner, JO et al., Lancet2:912, 1978) showed that by hyposensitizing subjects with a preparation of tick antigens, one could inhibit a delayed asthmatic reaction to inhaled tick antigens. Other studies have also shown that by hyposensitizing subjects with preparations of ragweed pollen, one could inhibit hypersensitive reactions during flowering seasons. Oral tolerance induction dates as far back as the early customs of the American Indians. Dakin (Dakin, R, Am. J. Med. Sci, 4:98, 1829) documents how lacquer artisans among the Indians fed their children small amounts of lacquer over an extended period of time to reduce the likelihood of being poisoned later in life. Patricia et al. (Patricia, G et al., Food Allergy, p.131, 1979) disclosed a method whereby patients allergic to milks, eggs, or fruits were given these items starting with very low amounts and gradually increasing the amounts over time. Others have since demonstrated the effectiveness of inducting oral tolerance using other foods. For food allergies, serious symptoms are usually caused by very small amounts of allergens, and so many foods are not amenable to the method prescribed by Patricia et al. Others have developed ways in which oral tolerance can still be induced without triggering an allergic responses to the allergen being used to induce tolerance. US patent 5863561 teaches a method for producing milk which contains allergens in a form that does not cause serious hypersensitive reactions but confers tolero-genic protection. The ability of many allergens administered orally to induce tolerance is destroyed by the digestive enzymes and functions of the gut. To overcome this limitation, others have found a way to deliver allergens to the gut while preserving their immunogenicity. US patent publication 20030003133 teaches a method to induce immune tolerance for common allergens by delivering allergens to the gut mucosa via milk. Presumably the milk protects the allergen against the degradative environment of the gastrointestinal tract. The limitation with this approach is that milk is required to delivery the allergen. US publication 20030180272 further teaches a method where probiotic bacteria are administered to children pre- and postnatally. Oral tolerance does not have to be limited to food allergen. Wells et al. (Wells, HG et al, J. Infect. Dis., 8:566, 1991) showed that when fed ovalbumin, normal guinea pigs would develop an immunological tolerance to ovalbumin. Other researchers have shown that when allergens are administered orally, they too induce immunological tolerance (Aramaki, Y et et, Immunol. Lett., 40:21, 1994) . For autoimmune diseases, the induction of oral tolerance can relieve symptoms of an over-aggressive immune system. Trentham et al. (Trentham, DE et al, Science, 261:1727, 1993) showed that by orally administering a preparation of Fowl II collagens to patients with rheumatoid arthritis, not only did the symptoms attenuate in many individuals, many of the patients recovered completely from their diseases. US patent publication 20030039666 further teaches the use of parasitic biological agents for prevention and control of auto-immune diseases. The methods described thus far induce tolerance via proactive administration of allergens to subjects subcutaneously, parenterally or orally. These methods have had limited adoption because they require significant behavioral changes on the part of the subject in order to acquire tolerance. That is, subjects must vigilantly take doses of allergens in a strictly prescribed manner over time before tolerance is achieved. Recent evidence suggests that certain environments protect against the primary development of allergic and autoimmune diseases. Strachan (Strachan, DP, British Medical Journal, 1989) showed epidemiologic data that increasing hygiene levels between populations is correlated to higher incidences of hay fever. This observation launched a series corroborating studies in Germany after the reunification in 1989. For example, von Mutius et al showed that in genetically similar populations, the prevalence of asthma and allergies was 164% higher among school children living in the former West (Munich) as compared with the children in former East Germany (Leipzig and Halle). Other studies demonstrating this East-West gradient and ruling out obvious factors such as pollution and tobacco use have since been published and are reviewed by L.C.von Hertzen and T.Haahtela (Hertzen, LC and Haahtela, T, Allergy 2004:59:124 -137). To explain these epidemiologic findings, a growing number of scientists proposed that the western lifestyle has succeeded in markedly decreasing the incidence of infections in early life, and these infections may have a protective effect on the subsequent development of allergies. Thus the decrease in the number of infections has resulted in an increase in risk for asthma, allergies and many autoimmune diseases later in life. This view led to the coining of the phrase the 'hygiene hypothesis' to explain the inverse relation between the incidence of infectious diseases and allergies. More recent findings have brought into question the role of early childhood infections in reducing allergies. Between 2000 and 2002 studies compared the asthma and allergy rates between populations of children with different infection rates. The results were contradictory. While some authors reported that contagious diseases such as measles were associated with decreased likelihood of developing allergic conditions, other researchers were unable to confirm these observations. Similar contradictory results were reported for other early childhood infectious diseases. The idea that tolerance is induced through infections has been largely discredited by these findings. However, a new area of research focusing on the farming environment has led to a revised statement of the hygiene hypothesis. While infections have been ruled out as the determining factor, studies have consistently found that growing up on farms is anticorrelated with development of asthma and allergies. Several of these studies showed that the best correlation factor in the prevalence of allergies among children living on farms and those living in the same rural villages, but not on a farm, was having contact with substances produced by farm animals (Von Ehrenstein et el., Braun-Fahrlander et al, Riedler et al., Ernst et al.). It is now known from molecular analysis that these substances are a blend of proteins (which are also allergens) ranging from lipopolysaccharides from bacterial cell wall to the major allergens of the cat, cow and chicken. It is also now known that these proteins have the unique ability to either induce tolerance against a wide variety of common allergens via cross-reactivity or suppress the Helper T cell Type 2 response (Helper T cell Type 2 are responsible for allergic sensitization). In other words, early and sustained exposure to these proteins allows the immune system to be more robust and tolerant of its environment. The finding that it is probably the exposure to animal proteins and possibly other proteins of non-animal origin, rather than infections, early in life that confers protection against allergic diseases presents an entirely new framework for understanding the hygiene hypothesis. It also provides an opportunity for the present invention which extends induced tolerance to new applications which are not limited to proactive administration of allergens. Specifically, the present invention improves on the existing methods to prevent primary development of allergic or autoimmune diseases by using common household or farm products and articles to release low dosages of proteins into the environment in such a way as to induce tolerance. By using such household or farm products, one can change the living environment of an infant human or mammalian farm animals to mimic the farming environments that have been significantly correlated with reduced disease risk. The immune system of a vertebrate mammalian animal such as a human being has two types of cells: T cell and B cells. In general, T cells kill microbes and B cells produce antibodies and these antibodies neutralize microbes or foreign matter. We will now use the term antigen in this application to refer to anything that is not a natural part the animal's body. Antigens therefore elicit an immune response. Any single T cell or B cell can only recognize a specific pattern on an antigen. That's why antibodies against snake venom will not neutralize bacteria. Similarly, a T cell that recognizes a particular flu strain will not recognize a different flu strain. Every single day, the body produces new T cells and B cells. The pattern a particular new T cell or B cell can recognize is determined through a random process where 1 out of about 6 billion patterns are selected for anew cell. Some of the 6 billion patterns are self-patterns. Self-patterns are patterns of normal animal tissue or parts of the animal body, so if the immune system cells recognize such cells, they would attack the cells which would lead to some sort of auto-immune disease. To prevent auto-immunity, immature immune cells that by chance get a self-pattern and recognize a natural part of the body are killed by the body while they are still immature. Killing of such immature cells does not produce an immune response in the body. At the end of each day, immune system cells that recognize self and non-self have been produced, and the self-recognizing cells have been mostly killed off to leave only non-self recognizing cells. There are many substances that are not naturally produced by the body, but are inhaled and/or ingested often. When the dose of the substances is great enough, the immune system cells which recognize them are killed off just as the cells which recognize self are killed off. Such substances do not provoke an immune response. Substances which are ingested rarely or occasionally in an insufficient dose where the immune system cells which would recognize have a chance to mature before meeting the substance may provoke an immune response from the now mature cells, which are not killed by the body if they recognize an intruder, and which may provoke an inflamation response which we characterize as an allergic response. We surmise that there domestic animals and humans in particular live in a much cleaner environment than previously, so that more types of immature immune system cells which would recognize strange patterns live to maturity. The way to prevent such allergies is to make sure that the body ingests a therapeutic dose of the common allergy inducing allergens before the body "becomes allergic" to them. In particular, we suggest that neo-natal vertebrate animals such as humans, domestic animals, and fish, be exposed to allergens before their immune systems are developed. We define a "neo-natal^" animal for the purposes of this specification as the animal from birth to the time when the animals immune system is fully developed. In humans, for example, babies are born with few antibodies of their own, and use the mother's antibodies for the first six weeks or so of their life. The critical period for human infants is the first three years of their life, although the immune system continues to develop and mature for a decade. A therapeutic dose of an antigen is a dose which leads to an antigen density in the body sufficient that an immature immune system cell would probably meet and recognize the antigen before it matures, and would hence be eliminated from the body before it matures to be part of the immune system. The most preferred embodiment of the invention is to provide antigens for the most common and dangerous allergies. In particular, allergies to peanuts appear very early in the life of human infants, as early as 1 year old. If the infant under the age of 1 is dosed regularly with a peanut antigen, such allergies will be avoided. Peanut (Arachis hypogaea) Among food allergies, peanut allergy is common and severe. Epidemiologic studies of the general population estimate a prevalence rate of 0.5%, and peanut allergy accounts forlO-47% of food- induced anaphylactic reactions. Symptoms may vary in severity from mild urticaria or localized oral symptoms, to severe systemic reactions that can be fatal. Reactions typically occur within a few minutes following ingestion. Peanut hypersensitivity usually begins in early childhood and usually persists throughout life, with only a small percentage of young children achieving tolerance. A novel method for providing a therapeutic dose of antigen sufficient to protect against allergies is to provide common articles of clothing, bedding, toys, or food with the antigen. In particular, baby clothes, bedding, and toys are proposed as carriers for such antigens. In addition, common substances such as baby powder and formula are admixed with sufficient antigen to give a therapeutic dose to the infant on a sufficiently regular basis that immune system cells recognizing the antigens would be unlikely to survive to maturity. Strips of material comprising a matrix holding an antigen are preferably sewn into clothing or blankets which are designed to be in close contact with the skin, so that the subjects ingest the antigen through the skin or by breathing. The strips preferably release their antigen in a continuous and controlled manner. The antigen material is preferably encapsulated in a coating which releases the antigen over time and/or upon certain events, such as washing or abrading the article. Such coatings are known, for example, in the art of controlled release drugs. In a preferred example, the encapsulation material is a polymer material. For example, the strips are constructed so that each washing of the article and associated strip exposes new antigen. Alternatively, material for bedding or clothing may be woven admixed with an antigen such as cat hair. Stuffed animal and other soft toys are particularly preferred as delivery vehicles for antigens. The antigens preferred for presenting are preferably antigens derived from materials chosen from the following list.

Cereal products Turkey meat (Meleagris gallopavo) Mouse Serum Proteins Mouse Urine Proteins

Barley (Hordeum vulgare ) Epithelia and Feather Pigeon Droppings

Buckwheat (Fagopyrum esculentum) Rabbit Epithelium

Gluten Budgie Droppings Rat (mix)

Maize (Zea mays) Budgie Feathers Rat Epithelium

Oats (Avena sativa) Budgie Serum Proteins Rat Serum Proteins

Rice (Oryza sativa) Cat Dander Rat Urine Proteins

Rye (Secale cereale) Cat dander / Cat saliva (Felis domesticus) Sheep Epithelium

Wheat (Triticum aestivum) Cat serum albumin Swine - serum albumin Chicken Feathers Swine Epithelium Drugs Cow - dander Cow Dander Fruits

Insulin Bovine Dog (Canis familiaris) Apple (Malus domestica)

Insulin Human Dog - serum albumin Apple

Insulin Porcine Dog Dander Apricot

Penicilloyl G Dog Epithelium Banana

Penicilloyl V Duck Feathers Blackberry

Suxamethonium (succinylcholine) Goat Epithelium (Rubus fruticosus) Goose Feathers Blueberry Egg and Fowl Guinea-pig Epithelium Carambola Chicken meat (Gallus spp Hamster Epithelium (Averrhoa carambola) Egg white Hedgehog (Erinaceus europaeus) Cherry Egg yolk Horse - epithelium / dander (Equus Cranberry

Hen's Egg White (Gallus domesticus) caballus) (Vaccinium oxycoccus, family Hen's Egg White: Ovomucoid Horse Dander Ericaceae) Ovalbumin Mouse (mix) Date (Phoenix dactylifera) Ovomucoid Mouse Epithelium Grape Grapefruit arundinacea) (Alopecurus pratensis)

Guava Cattail (Typhaceae) Meadow Foxtail grass (Alopecurus

Kiwi Fruit Chickling Vetch / Grass Pea / Blue Vetch pratensis)

(Actinidia chinensis) (Lathyrus sativus) Meadow grass (Poa pratensis)

Kiwi fruit Chicory Meadow grass / Kentucky Blue / June

Lemon (Cichor m intybus) grass

Lime Cocksfoot / Orchard (Dactyhs glomerata) (Poa pratensis)

Mandarin (Tangeπne.Clementine, Cocksfoot / Orchard (Dactyhs glomerata) Redtop (Agrostis stolomfera)

Satsumas) Cocksfoot grass / Dactyhs / Orchard Redtop / Bentgrass / Water Bent grass

Mango (Dactyhs glomerata) (Agrostis stolomfera / Agrostis

Melons Common reed lachnanthis)

Orange (Phragmites commums) Rye grass (Lohum perenne)

Papaya, Pawpaw Common Reed (grass) (Phragmites Rye-grass (Lohum perenne)

Passion fruit, Grenadilla commums) Salt grass (Distichhs spicata)

Peach Common wild oats Sedge Family (Cyperaceae)

Pear Common wild sorghum (Sorghum bicolor) Sedges /Nut grass

Persimmon (Khaki fruit, Sharon) (Diospyros Cottonwool grass (Imperata cyhndπca) Sweet Vernal grass kaki) Cultivated Oat (Anthoxanthum odoratum)

Pineapple (Avena sativa) Sweet vemal grass

Plum Cultivated oats (Anthoxanthum odoratum)

Strawberry (Fragaπa vesca) (Avena sativa) Timothy grass Cultivated rye (Phleum pratense) Grass Pollen (Secale cereale) Timothy grass Cultivated Rye grass (Secale cereale) (Phleum pratense)

Bahia grass Cultivated Wheat (Tπticum sativum) Timothy grass

(Paspalum notatum) English Bunch grass (Cenchrus cihaπs) (Phleum pratense)

Bahia grass False Oat grass (Arrhenatherum elat s) Velvet grass

(Paspalum notatum) Foxtail Millet (Holcus lanatus)

Barley pollen (Setaria ltahca) Velvet grass / Yorkshire Fog

(Hordeum vulgare) Grass Family (Poaceae) (Holcus lanatus)

Bermuda grass Hairy wild lettuce (Hypochoeπs radicata) Wild Rye Grass

(Cynodon dactylon) Johnson grass (Elymus tπticoides)

Bermuda grass (Sorghum halepense) Wild Rye grass

(Cynodon dactylon) Johnson grass (Elymus tπticoides)

Brome grass (Bromus mermis) (Sorghum halepense)

Brome grass / Rescue grass (Bromus Johnson grass Animal Venom inermis) (Sorghum halepense)

Bulbous Canary grass / Toowoomba Canary Kikuyu Bee moth grass (Phalaπs aquatica) (Pennisetum clandestinum) (Galleπa mellonella)

Bunny tail grass Maize pollen / Corn pollen (Zea mays) Berlin Beetle

(Lagurus ovatus) Meadow fescue (Trogoderma angustum (Solier))

Canary Grass (Festuca elatior) Blood Worm

(Phalaris arundinacea) Meadow Fescue grass (Festuca elator) (Chironomus thummi (C

Canary grass / Reed Canary grass (Phalaπs Meadow foxtail Blowfly (Calhphora stygia / Lucilia cuprina) (Ephestia cautella) Acarid mite

Brazilian fire ant (Solenopsis saevissima) Wasp (Polistes metricus) (Thyreophagus entomophagus) Caterpillar - Browntail moth Wasp (Polistes annularis) Acarus siro (storage mite) (Euproctis edwardsi) White faced Hornet Aleuroglyphus ovatus (Storage Mite) Cochineal (Dolichovespula maculata) Blomia kulagini (Storage mite)

(Dactylopius coccus) Worm (Ascaris suum) Blomia tjibodas Caloglyphus berlesei Cockroach Yellow Hornet (Dolichovespula arenaria) Ceflacor (Blatella germanica) Chortoglyphus arcuatus Colorado Potato Beetle Dermatophagoides farinae (HDM) Common clothes moth Legumes Dermatophagoides microceras (Tineola bisselliella) Carob (Ceratonia siliqua) (HDM)Dermatophagoides Common Wasp Guar, Guar gum (Cyamopsis pteronyssinus (HDM) / Pharinae (Vespula sp) tetragonolobus) (Dermatophagoides pteronyssinus)

Douglas fir tussock moth caterpillar (Orgyia Lentils (Lens esculenta) Dermatophagoides siboney pseudotsugata McDonnough) Pea (Pisum sativum) (HDM)Euroglyphus maynei (HDM) European Hornet Peanut (Arachis hypogaea) (Euroglyphus maynei) (Vespa crabro) Red Kidney bean Glycyphagus domesticus (Storage mite) Fire Ant (Phaseolus vulgaris) Hemisarcoptes cooremani

(Solenopsis invicta) Soyabean (Glycine max) House Dust Mite - D Giant Asian Hornet Tragacanth (Astragalus spp) House dust mite (HDM) (Vespa mandarina) White bean Lepidoglyphus destructor (Storage mite) Grain Weevil (Phaseolus vulgaris) Mites (Sitophilus granarius) Predatory mites (Phytoseiulus persimilis Green Nimitti Fly Meats and Milk / Hypoaspis miles) (Cladotanytarsus lewisi) Rabbit fur mite (Listrophorus gibbus) Honey Bee a-lactalbumin Scaly grain mite / Suidasia sp (Apis mellifera) Beef (Bos spp Storage Mite - Acarus siro (A

Horse Bot Fly (Gasterophilus intestinalis) b-lactoglobulin Storage Mite - Glycophagus domesticus Maggot / Asticot maggots (Calliphora Boiled Milk (Glycophagus) vomitoria) Casein Storage Mite - Lepidoglyphus

Mediterranean paper wasp Cheddar cheese destructor (Polistes do inulus) Cow's Milk (Bos domesticus) Storage Mite - Tyrophagus putrescens Midge (Chironomus thummi thummi / Cow's Milk Chironomus kiiensis) Cow's milk Whey Molds Mosquito (Aedes communis) Elk/Moose meat Northern fowl mite Goat's milk Alternaria alternata (tenuis) (Altemaria (Ornithonyssus sylvarium) Mare's milk alternata (tenuis)) Paper Wasp (Polistes spp Mould cheese Alternaria alternata (tenuis) (Alternaria Phospholipase Mutton (Ovis spp alternata (tenuis)) Pigeon feather mite Pork (Sus spp Alternaria alternata / tenuis (Alternaria (Diplaegidia columbae / Pterolichusl Rabbit (Oryctolagus spp alternata (A Tropical fire ant Aspergillus candidus (Solenopsis geminata) Mites Aspergillus fumigatus Warehouse moth Aspergillus niger Aureobasidium pullulans sinensis) Pumpkin seed Botrytis cinera Brazil Nut (Cucurbita pepo) Candida albicans (yeast) (Bertholletia excelsa) Red Kidney bean (Phaseolus vulgaris) Cephalosporium acremonium Broad bean / Vicia fava bean / Field bean Sesame / Sesame seed (Sesamum Cladosporium conidia (Vicia faba) indicum) Cladosporium herbarum Butter bean Soybean / Soya Bean (Glycine max) Coffee leaf rust (Hemileia vastatrix) (Phaseolus lunatus) Sugar bean Curvularea lunata Cashew nut Sugar Beet seed Epiccocum purpurascens (Anacardium occidentale (Beta vulgaris) Epicoccum purpurascens / nigrum Castor Bean Sunflower seed (Helianthus annuus) Fusarium moniliforme (Mold) (Ricinus communis) Walnut (Juglans spp Helminthosporium halodes Chestnut (Castanea sativa) Walnut (Juglans regia / nigra) Micropolyspora faeni (Saccharopolyspora Chickpea (Cicer arietinus) Walnut - processed rectivirgula) Coconut (Cocos nucifera) Mucor racemosus Cowpea / Black-eyed peas / Vigna bean Occupational Mushroom (Oyster) (Vigna senensis) (Pleurotus ostreatus) Fennel seed Amylase Penicillium notatum (Foeniculum vulgare) Castor bean Phoma betae Haricot Bean Chloramine-T / Chloramin T Pityrosporum obiculare Hazel nut (Corylus avellana) Ethylene Oxide Pityrosporum ovale / orbiculare Hazelnut (Corylus avellana) Ethylene oxide Rhizopus nigricans Hazelnut / Filbert / Barcelona Nut / Cob Formaldehyde / Paraformaldehyde

Silver moss / Reindeer moss / Reindeer Nut (Corylus avellana) Green Coffee bean lichen (Cladonia stellaris) Lentils (Lens culinaris / esculenta) Isocyanate HDI Spirulina (Arthrospira platensis) Lima bean (Phaseolus limensis) Isocyanate MDI Stachybotrys atra Linseed / Flaxseed (Linum usitatissimum) Isocyanate TDI Stemphylium botryosum Macadamia nut (Macadamia integrifolia / Ispaghula / Psillium / Psyllium Thermoactinomyces vulgaris Macadamia tetraphylla) (Plantago psyllium) Trichoderma viride Mung bean (Vigna radiata) Isphagula Trichophyton rubrum Nangai nut (Canarium indicum) Latex / Brazilian rubber tree (Hevea Ustilago nuda / tritici / maydis Peanut (Arachis hypogaea) braziliensis) Pecan nut Lysozyme Nuts, Seeds and Beans (Carya illinoensis) Phthalic anhydride Pecan Nut / Hickory Nut / Sweet Pignut Silk (Bombyx mori)Silk waste

Acorn nut (Carya illinoensis) Silk waste

Alfalfa / Lucerne / Medick Pine Nut / Pinon Nut / Pignoles / Pignola Trimellitic anhydride / TMA

Almond (Prunus dulcis) (Pinus edulis)

Almond (Prunus amygdalus) Pinto bean (Phaseolus vulgaris) Parasites

Almond Pistachio nut

(Amygdalus communis) (Pistachio vera) Anisakis

Besan / Garbanzo bean Poppy seed Anisakis / Cod Worm

Black bean (Phaseolus vulgaris) (Papaver somniferum) (Pseudoterranova)

Black turtle bean Pumpkin seed Ascaris

Black-eyed bean / Black-eye bean (Vigna (Cucurbita pepo) Ascaris lumbricoides / Common Roundworm (Ascaris lumbricoides) Black Pepper / White Pepper (Piper officinale)

Bilharzia / Schistosoma (Schistosomiasis / nigrum) Green Pepper (unripe seed)

Bilharziasis) Cacao - processed / Cocoa - processed Japanese Millet (Echinochloa crus-galli)

Echinococcus / Echinococcosis Capsanthin / Paprika extract Lavender

Entamoeba histolytica Caraway (Carum carvi) (Lavandula officinalis) Caraway (Carum carvi) Lovage Shellfish Cardamom / Cardemon (Elettaria (Levisticum officinale) cardamomum) Mace (Myristica fragrans)

Blue mussel Cardamon (Elettaria cardamomum) Marjoram

(Mytilus edulis) Celery seed (Origanum majorana)

Crab (Cancer pagurus) Chili peppers Mustard (Sinapis alba)

Fish - Mixed (Capsicum frutescens) Nutmeg

Hyssop Chilli Pepper / Chili pepper / Capsicum (Myristica fragrans)

Lobster (Capsicum genus) Nutmeg / Nutmeg oil (Myristica

(Homarus gammarus) Chives fragrans)

Octopus (Octopus vulgaris) (Allium schoenoprasum) Oregano

Oyster (Ostrea edulis) Cinnamon (Origanum vulgare)

Pacific Squid (Cinnamomum zeylanicum) Oriental mustard / Brajl (Brassica

(Todarodes pacificus) Clove juncea)

Shrimp (Natantia) (Syzygium aromaticum) Parsley

Shrimp (Pandalus borealis) Comffey (Petroselinum crispum)

Silverfish (Ctenolepisma longicaudata / (Symphytum officinale) Parsley

Lepisma saccharina) Coriander / Cilantro / Italian Parsley Pennyroyal oil / Squaw mint / Hedeoma

Snail (Helix aspersa) (Coriandrum sativum) Peppermint (Mentha x piperita)

Spiny Lobster (Langouste) (Palinurus spp Cumin / Cummin / Cumin oil (Cuminum Poppy Seed

Squid (Loligo spp cyminum) (Papaver somniferum) Curry (Santa Maria) Rosemary (Rosmarinus officinalis) Spices Curry leaf Rue (Ruta graveolens / Ruta montana L (Murraya koenigii) Saffron (Crocus sativus)

Allspice Curry powder / Santa Maria Sage (Salvia officinalis)

(Pimenta dioica (syn Dill (Anethum graveolens) Spearmint / Garden mint / Green mint

Allspice / Clove pepper / Jamaica pepper Fennel / Florence Fennel (Foeniculum (Mentha x spicata)

(Pimenta dioica / officinalis) vulgare) Star anise / Anis

Angelica / Angelic acid (Angelica Fenugreek (Trigonella foenum-graecum) (Ulicium verum) archangelica) Fenugreek / Greek Hay / Greek Fennel Tansy (Tanacetum vulgare)

Anise (Pimpinella anisum) (Trigonella foenum-graecum) Tarragon

Anise / Aniseed (Pimpinella anisum) Feverfew (Chrysanthemum parthenium) (Artemisia dracunculus)

Basil (Ocimum basilicum) Foxtail Millet Tarragon / Esdragol (Artemisia

Basil / Sweet Basil (Ocimum basilicum) (Setaria italica) dracunculus)

Bay Leaf (Laurus nobilis) Galangal root / Chinese ginger / East Thyme (Thymus vulgaris)

Bay leaf (Laurus nobilis) indian root Turmeric / Tumeric (Curcuma Ionga)

Bergamot / Bergamot Orange or Red / Garlic extract Vanilla (Vanilla planifolia)

Oswego tea Ginger (Zingiber officinale) Yarrow / Milfoil

Black Pepper Ginger spice / Ginger (fresh) (Zingiber (Achillea millefolium) Tree pollen Common silver birch (Betula verrucosa) Linden tree (Tilia cordata) Common Silver Birch tree Lindens (Tiliaceae)

Acacia (Acacia longifolia) (Betula verrucosa) London plane (Platanus acerifolia) Acacia tree / Wattle / Port JacksonAloe Vera Cork Loquat / Japanese medlar American beech (Fagus grandifolia) Cottonwood (Populus deltoides) (Eriobotry a j aponica) American chestnut tree Cottonwoods, Poplars, and Aspens Mango tree (Mangifera indica) (Castanea dentata) (Populus) Maple Family (Acer) American Elm (Ulmus americana) Date Palm tree (Phoenix dactylifera) Maple tree (Aceraceae) Apple tree (pollen) (Malus sylvestris) Douglas Fir tree (Pseudotsuga taxifolia) Maritime pine / Cluster pine Aroeira / Litre (Lithraea caustica) Eastern red cedar (Juniperus virginiana) (Pinus pinaster) Aroeira / Pao bugre Eastern white cedar (Thuja occidentalis) Melaleuca (Melaleuca leucadendron) (Lithraea brasiliensis) Elm Family (Ulmaceae) Melaleuca tea tree (Melaleuca

Australian pine tree / Casuarina (Pinus nigra Eucalyptus alternifolia) / Casuarina equisetifolia) European Chestnut tree (Castanea sativa) Mesquite (Prosopis juliflora) Bayberry Bark / Myrica Oil Ficus Milo wood (Thespesia populnea) Beech Family (Fagaceae) Flat tree / False Banana tree Mistletoe (Viscum album) Beechwood / Creosote (Platanus occidentalis) Molle (Lithraea molleoides) Bigonia Family (Bigononiaceae) Frangipani / Nosegay Mountain Cedar tree / Mountain Birch Family (Betualaceae) (Frangipani (Plumeria rubra)) Juniper tree (Juniperus sabinoides) Black Ash (Fraxinus nigra) Grey alder (Alnus incana) Mountain juniper (Juniperus Black Walnut Grey Alder tree sabinoides)

Blackwood tree (Acacia melanoxylon / (Alnus incana / Alnus glutinosa) Mulberry (Moms alba) Dalbergia melanoxylon) Guayule (Parthenium argentatum) Mulberry Family (Moraceae) Bottlebrush tree (Callistemonand melaleuca) Gum-tree / Eucalyptus / Cajeput t Mulberry tree (Morus Alba) Box elder (Acer negundo) Hackberry Oak (Quercus alba) Cabreuva tree (Myrocarpus fastigiatus) Hazel (Corylus avellana) Obache tree Camphor tree oil / Camphor oil / Japanese Hinoki tree / Finuchi tree Ohbayasyabushi Alder tree white oil Holly Family - Aquifoliaceae (Ilex opaca) (Alnus sieboldiana Matsuma)

Canary Island Date Palm tree Honey Locust tree / Mesquite tree Oleander / Oleander tea (Nerium (Phoenix canariensis) (Prosopsis juliflora) oleander) Carob / Locust Bean Gum / St Johns Bread Imbuia tree / Embuia tree / Olive Family (Oleaceae) (Ceratonia siliqua / Aka algarroba) Brazilian-Walnut tree (Phoebe Porosa) Palm Family (Palmae) Cashew Family (Anacardiaceae) Iroko tree / West African teak Paper Mulberry Cashew nut tree (Anacardium occidentale) (Milicia excelsa) Paperbark Tea Tree Cassia bark / Chinese cinnamon Italian cypress (Cupressus sempervirens) (Melaleuca quinquenervia) (Cinnamomum cassia) Italian Funeral Cypress tree (Cupressus Peach tree Cedar tree / Incense cedar (Libocedrus sempervirens) Pecan (Carya pecan) decurrens) Jacaranda (Jacaranda mimosifolia) Pecan tree / Hickory tree (Carya pecan /

Central American walnut Japanese cedar (Cryptomeria japonica) Carya illinoinensis) (Juglans olanchana) Japanese Cedar tree / Sugi tree Pepper tree (Schinus molle) Chestnut tree (Cryptomeria japonica) Pine tree / Norwegian Pine tree

Chinese chestnut tree (Castanea mollissima) Japanese chestnut (Castanea crenata) (Pinus radiata) Cigar Tree (B Juniper berry / Juniper oil Poplar tree / Cottonwood tree / Coconut (A (Juniperus communis) Matchwood (Populus deltoides / Alba) Populus (Cottonwoods, Poplars, and White pine (Pinus strobus) Fish - Mackerel (Scomber scombrus)

Aspens) Willow (Salix caprea) Fish - Megrim / Whiff/ White sole

Prickly Juniper tree Willow Family (Salicaceae) (Lepidorhombus whiffiagonis)

(Juniperus oxycedrus) Yellowood tree (Podocarpus Iatifolius) Fish - Pilchard (Sardina pilchardus)

Privet tree (Ligustrum vulgare) Zelkova tree Fish - Plaice (Pleuronectes platessa)

Prosopis tree (Zelkova carpinifolia / Zelkova serrata) Fish - Salmon (Salmo salar)

Putranjiva tree / Indian amulet tree Fish - Sardine (Sardinops melanosticta)

(Putranjiva roxburghii) Vegetables, salads, berries and Fish - Snapper

Quaking Aspen tree / Western Aspen tree some fish Fish - Snoek

(Populus tremuloides) Fish - Sole (Solea solea)

Queen Palm Abalone / Perloemoen (Haliotis midae) Fish - Swordfish (Xiphias gladius)

(Arecastrum romanzoffianum) Asparagus Fish - Trout (Oncorhynchus mykiss /

Red Alder Aubergine (Eggplant) Salmo gairdneri)

Red Cedar Avocado (Persea americana) Fish - Tuna (Thunnus albacares /

Red Maple Bamboo Shoot (Phyllostachys pubescens) thynnus)

Red or River Birch Barnacle (Crustacea) Fish - Western Australian salmon

Rosewood Blue Vetch (Mollusc) (Lathyrus sativus) (Arripis truttaceus)

Scotch Pine Broccoli Fish - Yellowtail (Seriola lalandii)

Shellbark Hickory (J Brown shrimp (Crustacea) Garlic (Allium sativum)

Sicilian sumac tree (Rhus coriaria L) (Penaeus aztecus) Gum Arabic (Acacia spp

Silky Oak (Grevillea robusta) Brussel Sprouts Lettuce

Silver Maple (A Saccharinum) Lobster (Crustacea) (Homarus

Spruce tree (Picea excelsa) Carrot gammarus)

Sugar date palm (Phoenix sylvestris) Cauliflower Malt

Sugar Maple (A Saccharinum) Celery Onion

Tibouchina tree / Princess-Flower / Glory Celery (Apium graveolens) Potato

Bush (Tibouchina) Crab (Crustacea) (Cancer pagurus) Pumpkin

Virginia live oak tree Crayfish / Crawfish (Crustacea) Scallop (Mollusc) (Pecten grandis)

(Quercus virginiana) Cucumber Scampi (Nephrops norvegicus)

Walnut (Juglans californica) Fennel, fresh (Foeniculum vulgare) Shrimp (Crustacea) (Pandalus borealis)

Walnut Family (Juglandaceae) Fish - Anchovis / Ansjovis Snails / Escargots (Helix aspersa)

Walnut tree (Juglans californica) (Engraulis capensis) Spinach

Weeping fig (Ficus benjamina) Fish - Bass Spiny Lobster / Langouste (Crustacea)

White Alder Fish - Bonito / Skipjack (Sarda sarda) (Panulirus vulgaris)

White Ash (Fraxinus americana) Fish - Chub Mackerel Squid (Mollusc)

White Ash (Fraxinus excelsior) (Scombridae japonicus) Sweet Potato

White Ash tree (Fraxinus americana / Fish - Cod (Gadus morhua) Tomato

Fraxinus excelsior) Fish - Eel (Anguilla anguilla)

White Birch Fish - Hake (Merluccius merluccius) Weed pollen

White cypress pine (Callitris glaucophylla) Fish - Halibut (Hippoglossus

White Elm tree (Ulmus americana) hippoglossus) Allscale

White Mulberry (M Fish - Herring (Clupea harengus) American Beech

White Mulberry Fish - Jack Mackerel / Shad / Scad American Elm

White Oak tree (Quercus alba) (Trachurus japonicus) American Sycamore Annual Mercury / Annual Dog's Mercury Marguerite (Mercurialis annua) (Chrysanthemum leucanthemum) Aster Family (Asteraceae) Mugwort (Artemisia vulgaris) Bishop's weed (Ammi majus) Mustard Family (Brassicaceae) Black Oak Nettle / Stinging Nettle (Urtica dioica) Burweed marshelder Orchard Grass Careless Weed Poison hemlock (Conium maculatum) Chrysanthemum spp Poison Ivy (Toxicodendron radicans) Cockelbur Rabbit Bush

Cocklebur (Xanthium commune) Ragweed - False (Franseria acanthicarpa) Cocklebur (Xanthium commune) Ragweed - Giant (Ambrosia trifida) Cocklebur (weed) Ragweed - Short / Ragweed - Common (Xanthium commune) Ragweed - Western (Ambrosia Common pigweed psilostachya) (Amaranthus retroflexus) Ramat / Garden Mum / Common ragweed (Ambrosia elatior) Rocket (Eruca sativa) Common Wormwood / Absinthe (Artemisia Rough Marsh Elder (weed) / Annual absinthium) Marshelder (Iva ciliata)

Dandelion (Taraxacum vulgare) Rough marshelder (Iva ciliata) Diplotaxis erucoides Russian thistle (Salsola kali (pestifer) English plantain (Plantago lanceolata) Sagebrush English Plantain (Plantago lanceolata) Sagebrush/Sage/Wormwood (Artemisia) False ragweed (Franseria acanthicarpa) Saltwort / Russian Thistle (Salsola kali Firebush (Kochia scoparia) (pestifer)) Gas plant / Burning bush Scale (Atriplex lentiformis) (Dictamnus albus) Scale / Saltbush / Lenscale Giant ragweed (Ambrosia trifida) (Atriplex lentiformis) Goatweed Shasta daisy (Chrysanthemum maximum)

Golden Rod / Goldenrod (weed) (Solidago Sheep sorrel (Rumex acetosella) virgaurea) Spiny sowthistle weed (Sonchus oleraceus)

Goosefood / Lamb's Quarter (Chenopodium Sunflower album) Thorn apple / Jimson weed / Jamestown

Goosefoot Family (Chenopodiaceae) weed (Datura stramonium) Hemp (Cannabaceae) Wall pellitory (Parietariajudaica) Hop Japanese Pollen / Japanese Hop Wall Rocket (Diplotaxis erucoides) (Humulus japonicus / Humulus scandens) Western ragweed (Ambrosia psilostachya) Horse nettle / Bull nettle / Radical weed White snakeroot (Eupatorium rugosum) (Solanum carolinense) Wormwood (Artemisia absinthium) Lambs Quarters (Chenopodium) Yellow Dock Leatherleaf fern / Leather fern / Bakers fern (Rumohra adiantiformis) Mala Mujer (Cnidoscolus angustidens) Mandrake (Mandragora officinarum / Mandragora autumnalis) U.S. Patents, U.S. patent publications, and other publications mentioned above are hereby incorporated herein by reference in their entirety including incorporated material. Obviously, many modifications and variations of the present invention are possible in light of the above teachings. It is therefore to be understood that, within the scope of the appended claims, the invention may be practiced otherwise than as specifically described. In particular, the inventors anticipate that antigens chosen from one family of materials will be protective against allergies to other classes of antigens, and these cross protection materials will be found in the course of ordinary experimentation as known to one in the art.

Claims

We claim:

1. A method, comprising:

a) exposing a mammalian animal with a dose of allergen, the dose sufficient to produce a therapeutic response in the mammalian animal, wherein the allergen is carried by a common material for exposing the mammalian animal.

2. The method of claim 1, wherein the common material releases allergen into the local environment of the mammalian animal.

3. The method of claim 1, wherein the mammalian animal is a human being.

4. The method of claim 3, wherein the common material is the material of an article of clothing.

5. The method of claim 3, wherein the common material is the material of an article of bedding.

6. The method of claim 3, wherein the common material is the material of a toy.

7. The method of claim 3, wherein the allergen is contained in a dusting powder, and the common material is dusted with the dusting powder.

8. The method of claim 4, wherein the common material is the material of a diaper.

9. The method of claim 1, wherein the mammal is an animal chosen from the group consisting of horses, cattle, pigs, goats, sheep, dogs, and cats.

10. The method of claim 9, wherein the common material is bedding material.

11. The method of claim 1, wherein the allergen is provided in a timed release form.

12. The method of claim 11, wherein the allergen is encapsulated within a coating.

13. The method of claim 12, wherein the coating is a polymeric coating..

14. A material, comprising;

a) a common material; and,

b) an allergen for exposing a mammalian animal, the common material carrying the allergen;

wherein exposing the mammalian animal with the common material and the allergen provides the mammalian animal with a dose of the allergen sufficient to produce a therapeutic response in the mammalian animal.

15. The material of claim 14, wherein the common material releases allergen into the local environment of the mammalian animal.

16. The material of claim 14, wherein the mammalian animal is a human being.

17. The material of claim 16, wherein the common material is the material of an article of clothing.

18. The material of claim 16, wherein the common material is the material of an article of bedding.

19. The material of claim 16, wherein the the common material is the material of atov.

20. The material of claim 16, wherein the allergen is contained in a dusting powder, and the common material is dusted with the dusting powder.

21. The material of claim 17, wherein the common material is the material of a diaper.

22. The material of claim 14, wherein the mammalian animal is an animal chosen from the group consisting of horses, cattle, pigs, goats, sheep, dogs, and cats.

23. The material of claim 22, wherein the common material bedding material.

24. The material of claim 14, wherein the allergen is provided in a timed release form.

25. The material of claim 24, wherein the allergen is encapsulated within a coating.

26. The material of claim 25, wherein the coating is a polymeric coating.

27. A method, comprising:

a) exposing a neo-natal vertebrate animal with a dose of allergen, the dose sufficient to produce a therapeutic response in the neo-natal vertebrate animal , wherein the allergen is carried by a common material for exposing the neo-natal vertebrate animal .

28. The method of claim 27, wherein the common material releases allergen into the local environment of the neo-natal vertebrate animal .

29. The method of claim 27, wherein the neo-natal vertebrate animal is a human being.

30. The method of claim 29, wherein the common material is the material of an article of clothing.

31. The method of claim 29, wherein the common material is the material of an article of bedding.

32. The method of claim 29, wherein the the common material is the material of a toy.

33. The method of claim 29, wherein the allergen is provided in dusting powder, and the common material is dusted with the dusting powder.

34. The method of claim 30, wherein the common material is the material of a diaper.

35. The method of claim 27, wherein the neo-natal vertebrate animal is an animal chosen from the group consisting of horses, cattle, pigs, goats, sheep, dogs, and cats.

36. The material of claim 35, wherein the common material bedding material.

37. The method of claim 27, wherein the allergen is provided in a timed release form.

38. The method of claim 37, wherein the allergen is encapsulated within a coating.

39. The method of claim 38, wherein the coating is a polymeric coating.