Immunotherapy: is there a place for recombinant allergens?

Specific immunotherapy is the sole etiologic mode of treatment in allergic diseases, leading to modulation of the immune response against allergens. Extracts of natural allergen sources currently used in clinical practice are heterogeneous and their composition and content in major and minor allergens are variable. Cloning of allergenic proteins is the starting point for the development of recombinant allergens offering new therapeutic perspectives in immunotherapy, In conventional immunotherapy the use of recombinant allergens should allow the adequate adaptation of immunotherapy to the specific IgE sensitization of each allergic patient and the quantification of the dosage of major and minor allergens in allergen preparations. The use of peptides and engineered hypoallergens for immunotherapy should lead to better efficacy and greater safety by reducing the risk of anaphylactic side reactions. Over the last 5 years, several studies have been performed with peptides and modified recombinant allergens derived from the most important allergens, using various approaches: treatment with peptides representing a portion of T cell epitopes. selection of isoforms of allergen molecules identified on the basis of low/no IgE binding activity, production of hypoallergenic derivatives using recombinant technology (allergenic fragments and recombinant oligomers where conformational B epitopes are lost or hidden, modification of important amino-acid sequences by site-directed mutagenesis and destruction of disulfide bonds either in IgE binding epitopes or at sites outside the epitopes influencing the conformation of the molecules and thereby the IgE binding activity), synthesis of peptides corresponding to portions of B cell epitopes, All these engineered hypoallergens have been selected by experimental animal studies and in vitro studies using T lymphocytes from allergic patients, and sera to assess loss of IgE reactivities by RAST-EIA and IgE inhibition assay; in vivo studies were also performed in sensitized patients using cutaneous tests. Desensitization efficacy studies were only performed with peptides derived from T cell epitopes. (C) 2002 Editions scientifiques et medicales Elsevier SAS.