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
Source: PubMed


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.

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    • "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) [54], olive pollen (Ole e 1) [55], and the Alternaria alternata mould [56] 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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