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Recombinant allergens

The techniques of genetic engineering applied to allergens have enabled the production of recombinant allergens (RAs). Many of the problems associated with using natural allergenic products for allergy diagnosis and treatment can be overcome with use of genetically engineered recombinant allergens. Over the past 10 years, the most important allergens from mites, pollens, animal dander, insects, and foods have been cloned, sequenced, and expressed in heterologous hosts (e.g., Escherichia coli), their cDNA being used as a template. In many cases the three-dimensional allergen structure has been determined and B-cell and T-cell epitopes have been mapped.

These studies show that allergens have diverse biologic functions (they may be enzymes, enzyme inhibitors, lipocalins, or structural proteins) and that as a rule the allergen function is unrelated to its ability to cause IgE antibody responses. High-level expression systems have been developed to produce recombinant allergens in bacteria, yeast, or insect cells. Recombinant allergens show comparable IgE antibody binding to their natural counterparts (where available) and show excellent reactivity on skin testing and in in vitro diagnostic tests.

Cocktails of recombinant allergens can be formulated with predetermined and uniform allergen levels, which could replace natural allergens and result in the development of innovative, patient-based tests for allergy diagnosis. Recombinant allergens also offer the exciting possibility of developing new forms of allergen immunotherapy, including the use of hypoallergens, allergens coupled to IgE suppressive adjuvants, and peptide-based therapies. The production of recombinant allergens as defined molecular entities makes it feasible to consider the possibility of developing prophylactic allergen vaccines [1]. Therefore new strategies have been developed to reduce the allergenic potential of recombinant allergens.

Peptide chemistry and recombinant DNA technology have allowed production of T cell epitope- and Bcell epitope-containing peptides, recombinant allergen isoforms, mutants, fragments as well as recombinant allergen oligomers with reduced allergenic activity [2, 3, 4, 5]. Heiss  et al 1999 demonstrated that recombinant allergens can be used for component-resolved skin test diagnosis (CRD) of the patients' allergen sensitization profile, whereas allergen extracts at best allow to identify allergen-containing sources. CRD may thus represent the basis for novel forms of patient-tailored immunotherapy. The in vitro diagnostic value of recombinant allergens depends on the correlation between allergen specific IgE in serum and ability of the protein to elicit immediate type allergic reactions in sensitized individuals[6].

The introduction of recombinant allergens in research and in clinical trials should lead to significant improvements in allergy diagnosis and treatment.

1. Chapman MD, Smith AM, Vailes LD, Arruda LK, Dhanaraj V, Pomes A Recombinant allergens for diagnosis and therapy of allergic disease. J Allergy Clin Immunol 2000 Sep;106(3 Pt 1):409-418 .

2. Oldfield WL, et al: Allergen-derived T cell peptide-induced late asthmatic reactions precede the induction of antigen-specific hyporesponsiveness in atopic allergic asthmatic subjects. J Immunol 2001:167:1734-1739.

3. Valenta R, et al: Recombinant allergens. Allergy 1998:53:552-561.

4. Valenta R, et al: The recombinant allergen-based concept of component-resolved diagnostics and immunotherapy (CRD and CRIT). Clin Exp Allergy 1999:29:896-904.

5. Valenta R, et al:  Inflammatory mechanisms in allergic diseases. In. Zweiman, B, Schwartz, LB, editors. Synthetic and Genetically Engineered Allergen Derivatives for Specific Immunotherapy of Type 1 Allergy. New York, Basel: Marcel Dekker Inc, 2000, 495-517.

6. Heiss, S., Mahler V., Spitzauer S., et al.  Component-Resolved Diagnosis (CRD) of Type I Allergy with Recombinant Grass and Tree Pollen Allergens by Skin Testing. Journal of Investigative Dermatology. 1999:113:5: 830 -

Γκέλης Ν.Δ. - Λεξικό Αλλεργίας - Εκδόσεις ΒΕΛΛΕΡOΦΟΝΤΗΣ - Κόρινθος 2013

Gelis Ν.D. - Dictionary of Allergies - VELLEROFONTIS Publications - Corinth 2013