Allergen extracts: Composition, manufacture, and labeling
- Robert E Esch, PhD
Robert E Esch, PhD
- Adjunct Professor, School of Natural Sciences
- Lenoir-Rhyne University
Allergens in this topic review will be defined as molecules capable of eliciting immunoglobulin E (IgE)-mediated hypersensitivity reactions. Allergen extracts are used in a variety of diagnostic and therapeutic applications, including diagnostic skin testing, provocation testing, and in vitro tests, as well as allergen-specific immunotherapy (both oral and subcutaneous). In all applications, the active ingredient is theoretically the relevant allergens from that source, although the formulation may differ between applications.
The production and standardization of allergen extracts are discussed in this topic review. The choice of specific extracts for use in clinical practice and other issues related to the use of allergen extracts are reviewed in more detail separately. (See "SCIT: Preparation of allergen extracts for therapeutic use", section on 'Types of allergen extracts' and "SCIT: Standard schedules, administration techniques, and monitoring".)
COMPONENTS OF ALLERGEN EXTRACTS
Allergen extracts are complex mixtures of allergenic and nonallergenic substances, including proteins, glycoproteins, polysaccharides, lipids, nucleic acids, low molecular weight metabolites, salts, and pigments. Most allergens are proteins or glycoproteins, but in certain rare circumstances, pure carbohydrates or low molecular weight chemicals can act as allergens. All foreign proteins are potential allergens in theory, although only a limited number of proteins are confirmed to be allergenic in humans. No structural properties have been identified that distinguish allergenic from nonallergenic proteins.
Allergen extracts are usually prepared by aqueous extraction of allergenic source materials obtained from natural sources. The composition and biologic properties may be influenced by the quality and purity of the source material, as well as their processing, extraction, and storage conditions. For batch-to-batch consistency, it is sufficient to consider the proteins as active ingredients.
Crude aqueous allergen extracts containing all of the extractable components of the source material can be used without further modification or subjected to further processing, including fractionation, physicochemical modification, and combination with other allergen extracts . Most commercially available extracts are crude extracts.
- Hauck PR, Williamson S. The manufacture of allergenic extracts in North America. Clin Rev Allergy Immunol 2001; 21:93.
- King TP, Hoffman D, Løwenstein H, Marsh DG, Platts-Mills TAE, Thomas W. Allergen Nomenclature, J Allergy Clin Immunol 1995; 96:5.
- Esch RE. Allergen source materials and quality control of allergenic extracts. Methods 1997; 13:2.
- Slater JE, Esch RE. Preparation and standardization of allergen extracts. In: Allergy: Principles and practice, 8th ed, Adkinson NF, Bochner BS, Burks W, et al (Eds), Mosby, Philadelphia 2014. p.470.
- Wahn U, Siraganian RP. Efficacy and specificity of immunotherapy with laboratory animal allergen extracts. J Allergy Clin Immunol 1980; 65:413.
- Bunyavanich S, Donovan MA, Sherry JM, Diamond DV. Immunotherapy for mouse bite anaphylaxis and allergy. Ann Allergy Asthma Immunol 2013; 111:223.
- Marsh DG, Norman PS, Roebber M, Lichtenstein LM. Studies on allergoids from naturally occurring allergens. III. Preparation of ragweed pollen allergoids by aldehyde modification in two steps. J Allergy Clin Immunol 1981; 68:449.
- Lüderitz-Püchel U, Keller-Stanislawski B, Haustein D. Neubewertung des Risikos von Test- und Therapieallergenen. Bundesgesundheitsbl-Gesundheitsforsch-Gesundheitsschutz 2001; 44:709.
- Norman PS, Ohman JL Jr, Long AA, et al. Treatment of cat allergy with T-cell reactive peptides. Am J Respir Crit Care Med 1996; 154:1623.
- Pfaar O, Biedermann T, Klimek L, et al. Depigmented-polymerized mixed grass/birch pollen extract immunotherapy is effective in polysensitized patients. Allergy 2013; 68:1306.
- Patel D, Couroux P, Hickey P, et al. Fel d 1-derived peptide antigen desensitization shows a persistent treatment effect 1 year after the start of dosing: a randomized, placebo-controlled study. J Allergy Clin Immunol 2013; 131:103.
- Butler NR, Voyce MA, Burland WL, Hilton ML. Advantages of aluminium hydroxide adsorbed combined diphtheria, tetanus, and pertussis vaccines for the immunization of infants. Br Med J 1969; 1:663.
- Mellerup MT, Hahn GW, Poulsen LK, Malling H. Safety of allergen-specific immunotherapy. Relation between dosage regimen, allergen extract, disease and systemic side-effects during induction treatment. Clin Exp Allergy 2000; 30:1423.
- Marrack P, McKee AS, Munks MW. Towards an understanding of the adjuvant action of aluminium. Nat Rev Immunol 2009; 9:287.
- al-Shakhshir RH, Regnier FE, White JL, Hem SL. Contribution of electrostatic and hydrophobic interactions to the adsorption of proteins by aluminium-containing adjuvants. Vaccine 1995; 13:41.
- Rosewich M, Lee D, Zielen S. Pollinex Quattro: an innovative four injections immunotherapy in allergic rhinitis. Hum Vaccin Immunother 2013; 9:1523.
- Akdis CA, Blaser K. Regulation of specific immune responses by chemical and structural modifications of allergens. Int Arch Allergy Immunol 2000; 121:261.
- Ferreira F, Briza P, Inführ D, et al. Modified recombinant allergens for safer immunotherapy. Inflamm Allergy Drug Targets 2006; 5:5.
- Larsen JN, Houghton CG, Vega ML, Løwenstein H. Manufacturing and standardizing allergen extracts in Europe. Clin Allergy Immunol 2008; 21:283.
- Slater JE. Standardized allergen vaccines in the United States. Clin Allergy Immunol 2008; 21:273.
- van Ree R, Chapman MD, Ferreira F, et al. The CREATE project: development of certified reference materials for allergenic products and validation of methods for their quantification. Allergy 2008; 63:310.
- Seppälä U, Dauly C, Robinson S, et al. Absolute quantification of allergens from complex mixtures: a new sensitive tool for standardization of allergen extracts for specific immunotherapy. J Proteome Res 2011; 10:2113.
- Turkeltaub PC. Biological standardization based on quantitative skin testing--the ID50 EAL method (intradermal dilution for 50 mm sum of erythema diameters determines the allergy unit). Arb Paul Ehrlich Inst Georg Speyer Haus Ferdinand Blum Inst Frankf A M 1987; :169.
- Nordic Council on Medicines. Registration of allergen preparations: Nordic guidelines. NLN Publication No 23, 1989, p.1.
- COMPONENTS OF ALLERGEN EXTRACTS
- Major allergens
- The paradox of extract refinement
- SOURCE MATERIALS FOR ALLERGEN EXTRACTS
- Other materials
- - Fungi
- - Animals
- - Insects and house dust mites
- House dust mite
- Hymenopteran venoms
- Fire ant whole body extracts
- Accounting for natural variability
- MANUFACTURE OF ALLERGEN EXTRACTS
- Extraction and quality control of allergen extracts
- - Recombinant allergens
- Formulations of allergen extracts
- Modification of extracts
- - Chemical modification (allergoids)
- - Coupling with inorganic gels
- - Molecular modification
- - Special considerations for different routes of administration
- STANDARDIZATION OF ALLERGEN EXTRACTS
- UNITS OF MEASURE
- Units that do not reflect potency
- Units that reflect potency
- - Bioequivalent allergy unit
- - Biologic unit
- CHOOSING EXTRACTS FOR USE IN PRACTICE
- ALLERGEN EXTRACT PRODUCTION AROUND THE WORLD
- SOCIETY GUIDELINE LINKS