Recombinant allergens: What does the future hold?

Christian Doppler Laboratory for Allergy Research, Medical University of Vienna, Vienna, Austria.
The Journal of allergy and clinical immunology (Impact Factor: 11.48). 04/2011; 127(4):860-4. DOI: 10.1016/j.jaci.2011.02.016
Source: PubMed


This year we are celebrating not only the centenary of allergen-specific immunotherapy but also the 10-year anniversary of the first administration of recombinant allergen-based vaccines to allergic patients. By using recombinant DNA technology, defined and safe allergy vaccines can be produced that allow us to overcome many, if not all, of the problems associated with the use of natural allergen extracts, such as insufficient quality, allergenic activity, and poor immunogenicity. Here we provide an update of clinical studies with recombinant allergen-based vaccines, showing that some of these vaccines have undergone successful clinical evaluation up to phase III studies. Furthermore, we introduce a strategy for allergen-specific immunotherapy based on recombinant fusion proteins consisting of viral carrier proteins and allergen-derived peptides without allergenic activity, which holds the promise of being free of side effects and eventually being useful for prophylactic vaccination.

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    • "DNA technology has already been employed for the preparation of vaccines, overcoming many of the problems associated with the use of natural allergen extracts, such as insufficient quality, allergenic activity, and poor immunogenicity. Numerous clinical trials have also demonstrated the many advantages of allergen-specific immunotherapy over conventional pharmacotherapy [17]. "
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    ABSTRACT: Treatment of patients suffering from chronic diseases such as rheumatoid arthritis with recombinant antibodies is time consuming and fairly expensive and can be associated with side effects due to generalized depletion of the target molecule. We have addressed these issues by developing an alternative approach consisting of the intraarticular injection of a DNA vector encoding for the anti-C5 neutralizing recombinant miniantibody MB12/22. This method allows local production of the antibody in sufficient amount to be effective in preventing joint inflammation in a rat model of antigen-induced arthritis. Injection of the DNA vector in a right knee of normal rats resulted in the production of the minibody detected in the synovial washes by western blot with a strong signal peaking at 3 days after administration. DNA encoding for the minibody was shown for 14 days in the synovial tissue and was undetectable in the controlateral knee and in other organs. The preventive effect of this approach was evaluated in rats receiving a single injection of the vector 3 days before the induction of antigen-induced arthritis and analyzed 3 days later. The treated rats exhibited a lower increase in swelling, associated with a lower number of PMN in the articular washes and reduced deposition of C9 in synovial tissue compared to control rats. These results suggest that treating the inflamed joints with a vector that induces a local production of a neutralizing anti-C5 antibody may represent a useful strategy to inhibit in situ complement activation and to treat patients with monoarthritis. Moreover, this approach may be adopted as a novel therapeutic strategy to prevent monoarthritis as an alternative to local treatment with antibodies commonly used in this form of arthritis, with the advantages of the lower cost and the longer persistence of antibody production.
    Full-text · Article · Mar 2013 · PLoS ONE
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    • "Les études cliniques d'ITA utilisant des allergènes recombinants, modifiés ou non, ont été répertoriées dans une revue récente de Rudolph Valenta [39]. Les rares études de phase 2 ou 3 en double aveugle contre placébo (DACP) ayant fait l'objet d'une publication concernent l'allergie au bouleau, l'allergie aux graminées et plus récemment une étude sur l'allergie au chat. "
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    ABSTRACT: Identification of culprit allergens is important for prophylactic measures and specific allergen immunotherapy (SIT). Since the late 1980s, the use of molecular cloning technology has led to a major improvement in our knowledge of epitopes involved in IgE-mediated allergy, and has also allowed in vitro production of recombinant allergens of interest for the diagnosis of allergenic sensitization. It has also improved our understanding of allergen cross-reactivity, which can be responsible for severe clinical manifestations, particularly in children with food allergy and allergic asthma. Better knowledge of molecular and cellular mechanisms of allergenic sensitization, based on the use of natural or modified recombinant allergens, has led to the development of effective SIT strategies which, in the foreseeable future, could provide genuine cure, therefore avoiding use of symptomatic therapeutics, starting very early in childhood.
    Full-text · Article · Mar 2013 · Bulletin de l'Académie nationale de médecine
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    • "The only proven and effective treatment is to conduct a diet free of fish and their derivatives. However, new developments in the characterization of epitopes on fish allergens are becoming the target for the development of novel diagnostic tools and specific immunotherapies [4] [5] [6]. Fish-sensitive patients are commonly allergic to numerous fish species [7]. "
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    ABSTRACT: Parvalbumins beta (β-PRVBs) are considered the major fish allergens. A new strategy for the rapid and direct detection of these allergens in any foodstuff is presented in this work. The proposed methodology is based on the purification of β-PRVBs by treatment with heat, the use of accelerated in-solution trypsin digestion under an ultrasonic field provided by High-Intensity Focused Ultrasound (HIFU) and the monitoring of only nineteen β-PRVB peptide biomarkers by Selected MS/MS Ion Monitoring (SMIM) in a linear ion trap (LIT) mass spectrometer. The present strategy allows the direct detection of the presence of fish β-PRVBs in any food product in less than 2 hours.
    Full-text · Article · Apr 2012 · Journal of proteomics
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