Carrier-Bound Alt A 1 Peptides without Allergenic Activity for Vaccination Against Alternaria Alternata Allergy
Christian Doppler Laboratory for Allergy Research, Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria. Clinical & Experimental Allergy
(Impact Factor: 4.77).
06/2012; 42(6):966-75. DOI: 10.1111/j.1365-2222.2012.03996.x
The mould Alternaria alternata is a major elicitor of allergic asthma. Diagnosis and specific immunotherapy (SIT) of Alternaria allergy are often limited by the insufficient quality of natural mould extracts.
To investigate whether recombinant Alt a 1 can be used for reliable diagnosis of Alternaria alternata allergy and to develop a safe, non-allergenic vaccine for SIT of Alternaria allergy.
The qualitative sensitization profile of 80 Alternaria-allergic patients from Austria and Italy was investigated using an allergen micro-array and the amount of Alternaria-specific IgE directed to rAlt a 1 was quantified by ImmunoCAP measurements. Peptides spanning regions of predicted high surface accessibility of Alt a 1 were synthesized and tested for IgE reactivity and allergenic activity, using sera and basophils from allergic patients. Carrier-bound peptides were studied for their ability to induce IgG antibodies in rabbits which recognize Alt a 1 and inhibit allergic patients' IgE reactivity to Alt a 1.
rAlt a 1 allowed diagnosis of Alternaria allergy in all tested patients, bound the vast majority (i.e. >95%) of Alternaria-specific IgE and elicited basophil activation already at a concentration of 0.1 ng/mL. Four non-allergenic peptides were synthesized which, after coupling to the carrier protein keyhole limpet hemocyanin, induced Alt a 1-specific IgG and inhibited allergic patients' IgE binding to Alt a 1.
rAlt a 1 is a highly allergenic molecule allowing sensitive diagnosis of Alternaria allergy. Carrier-bound non-allergenic Alt a 1 peptides are candidates for safe SIT of Alternaria allergy.
Figures in this publication
Available from: Margarete Focke-Tejkl
- "This vaccine design was evaluated with peptides derived from the major allergens from timothy grass pollen (Phl p 1 and Phl p 5) [52, 53•], birch pollen (Bet v 1) , olive pollen (Ole e 1) , and the Alternaria alternata mould  by chemical coupling to keyhole limpet hemocyanin as carrier. Vaccination of mice and rabbits induced specific IgG antibodies that were able to inhibit the binding of IgE of allergic patients to the natural allergens. "
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ABSTRACT: Opinion statement
Allergic diseases are among the most common health issues worldwide. Specific immunotherapy has remained the only disease-modifying treatment, but it is not effective in all patients and may cause side effects. Over the last 25 years, allergen molecules from most prevalent allergen sources have been isolated and produced as recombinant proteins. Not only are these molecules useful in improved allergy diagnosis, but they also have the potential to revolutionize the treatment of allergic disease by means of immunotherapy. Panels of unmodified recombinant allergens have already been shown to effectively replace natural allergen extracts in therapy. Through genetic engineering, several molecules have been designed with modified immunological properties. Hypoallergens have been produced that have reduced IgE binding capacity but retained T cell reactivity and T cell peptides which stimulate allergen-specific T cells, and these have already been investigated in clinical trials. New vaccines have been recently created with both reduced IgE and T cell reactivity but retained ability to induce protective allergen-specific IgG antibodies. The latter approach works by fusing per se non-IgE reactive peptides derived from IgE binding sites of the allergens to a virus protein, which acts as a carrier and provides the T-cell help necessary for immune stimulation and protective antibody production. In this review, we will highlight the different novel approaches for immunotherapy and will report on prior and ongoing clinical studies.
- "The main principle of peptides coupled to carriers (i.e. rhinovirus-derived coat proteins VP1, PreS domain of hepatitis) is the reduction of immediate and late phase reactions during treatment, together with the stimulation of carrier-specific T cells, which provide help for the induction of blocking IgG antibodies [212–215] (Fig. 4). In addition, the production of regulatory T cells leading to permanent tolerance is also investigated . "
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ABSTRACT: The first adverse reactions to cow's milk were already described 2000 years ago. However, it was only 50 years ago that several groups started with the analysis of cow's milk allergens. Meanwhile the spectrum of allergy eliciting proteins within cow's milk is identified and several cow's milk allergens have been characterized regarding their biochemical properties, folding and IgE binding epitopes. The diagnosis of cow's milk allergy is diverse ranging from fast and cheap in vitro assays to elaborate in vivo assays. Considerable effort was spent to improve the diagnosis from an extract-based into a component resolved concept. There is still no suitable therapy available against cow's milk allergy except avoidance. Therefore research needs to focus on the development of suitable and safe immunotherapies that do not elicit severe side effect.
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ABSTRACT: In 2010 over 200 articles were published in Clinical and Experimental Allergy including editorials, reviews, opinion articles, letters, book reviews and of course at the heart of the journal, papers containing original data which have moved the field of allergy forward on a number of fronts. For the third year running the editors felt it would be of value to summarize the key messages contained in these papers as a snapshot of where the cutting edge of research into allergic disease is leading. We have broadly followed the sections of the journal, although this year the mechanistic articles are grouped together and the studies involving experimental models of disease are discussed throughout the paper. In the field of asthma and rhinitis phenotypes and biomarkers continue to a major pre-occupation of our authors. There is continued interest in mechanisms of inflammation and disordered lung function with the mouse model of asthma continuing to offer new insights. There is also a steady flow of papers investigating new therapies, including those derived from plants and herbs, although many are mechanistic with too few high quality clinical trials. The mechanisms involved in allergic disease are well covered with many strong papers using clinical material to ask relevant questions. Pro-pre and snybiotics continue to be of major interest to our authors and this remains a controversial and complicated field. The discipline of epidemiology has retained its interest in risk factors for the development of allergic disease with a view to refining and debating the reasons for the allergy epidemic. There is continued interest in the relationship between helminthic disease and allergy with a new twist in 2010 involving studies using infection with helminths as a potential treatment. The genetics of allergic disease continues to be very productive, although the field has moved on from only investigating single nucleotide polymorphisms of candidate genes to Genome Wide Association Studies and an increasing and welcome emphasis on gene-environment interactions. In the field of clinical allergy there is steady flow of papers describing patterns of drug allergy with renewed interest in reactions to contrast media, but food allergy is the major area of interest in this section of the journal. Lastly in the field of allergens there is a growing interest in the role of component resolved diagnosis in improving the diagnosis and management of allergic disease. Another excellent year, full of fascinating and high quality work, which the journal has been proud to bring to the allergy community.
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