title: Modified recombinant allergens for safer immunotherapy.
abstract: Molecular cloning and recombinant production of allergens offered new perspectives for the increasing problem of allergies. A variety of preparations are being developed aiming to increase safety and improve efficacy of specific immunotherapy. Recombinant-based approaches are mostly focused on genetic modification of allergens to produce molecules with reduced allergenic activity and conserved antigenicity, i.e. hypoallergens. Studies dealing with genetic modifications of allergen genes reported the production of site-directed mutants, deletion mutants, allergen fragments and oligomers, and allergen chimeras. An alternative to genetic engineering is the chemical modification of pure recombinant allergens. It has been shown that allergens modified with immunostimulatory DNA sequences (allergen-ISS conjugates), which masks IgE epitopes and adds a desirable Th1-inducing character to the allergen molecule. Other chemical modifications include oligomerization by aldehydes (allergoids) and maleylation, which seems to target allergens to particular antigen presenting cells. Several of these modified allergen preparations have been already evaluated for their safety in clinical provocation studies. So far, clinical trials showed the efficacy and safety of immunotherapy with an Amb a 1-ISS conjugate for ragweed pollen-allergic patients. In addition, a preparation consisting of hypoallergenic fragments of Bet v 1 was evaluated for immunotherapy of birch pollen-allergic patients. In parallel, several animal studies have now demonstrated the potential of genetic immunization for allergy treatment in the future.
authors.affiliation: Department of Molecular Biology, University of Salzburg, A-5020 Salzburg, Austria. fatima.ferreira@sbg.ac.at
authors.forename: Fátima
authors.initials: F
authors.lastname: Ferreira
authors.forename: Peter
authors.initials: P
authors.lastname: Briza
authors.forename: Daniela
authors.initials: D
authors.lastname: Inführ
authors.forename: Georg
authors.initials: G
authors.lastname: Schmidt
authors.forename: Michael
authors.initials: M
authors.lastname: Wallner
authors.forename: Nicole
authors.initials: N
authors.lastname: Wopfner
authors.forename: Josef
authors.initials: J
authors.lastname: Thalhamer
authors.forename: Gernot
authors.initials: G
authors.lastname: Achatz
mesh_terms: D000485:Allergens / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use*; D000818:Animals; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects; D015202:Protein Engineering; D011994:Recombinant Proteins / Q000627:therapeutic use*; D019444:Vaccines, DNA / Q000627:therapeutic use
chemical_list: D000485:Allergens; D011994:Recombinant Proteins; D019444:Vaccines, DNA