Modified Recombinant Allergens for Safer Immunotherapy

Author(s): Fatima Ferreira , Peter Briza , Daniela Infuhr , Georg Schmidt , Michael Wallner , Nicole Wopfner , Josef Thalhamer , Gernot Achatz .

Journal Name: Inflammation & Allergy - Drug Targets (Discontinued)

Volume 5 , Issue 1 , 2006

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, whi ch seems to target allergens to paarticular 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.

Keywords: Recombinant allergen, IgE epitope, T cell epitope, allergen vaccines, specific immunotherapy, hypoallergen, genetic engineering, DNA vaccines

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Article Details

VOLUME: 5
ISSUE: 1
Year: 2006
Page: [5 - 14]
Pages: 10
DOI: 10.2174/187152806775269295

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