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Differences in the intrinsic immunogenicity and allergenicity of B et v 1 and related food allergens revealed by site‐directed mutagenesis
Author(s) -
Roulias A.,
Pichler U.,
Hauser M.,
Himly M.,
Hofer H.,
Lackner P.,
Ebner C.,
Briza P.,
Bohle B.,
Egger M.,
Wallner M.,
Ferreira F.
Publication year - 2014
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12306
Subject(s) - immunogenicity , hypoallergenic , allergy , allergen , mutagenesis , chemistry , immunoglobulin e , cysteine , food allergy , adjuvant , mutant , antibody , immunology , biology , biochemistry , gene , enzyme
Abstract Background Birch pollen allergies are frequently associated with adverse reactions to various fruits, nuts, or vegetables, described as pollen–food syndrome ( PFS ) and caused by cross‐reactive IgE antibodies primarily directed against B et v 1. Specific immunotherapy ( SIT ) represents an effective treatment for inhalant allergies; however, successful birch pollen SIT does not correlate well with the amelioration of concomitant food allergies. Methods As vaccine candidates, apple M al d 1 as well as hazelnut C or a 1 derivatives were designed by in silico backbone analyses of the respective allergens. The proteins were produced by site‐directed mutagenesis as fold variants of their parental allergens. Because M al d 1 and C or a 1 form cysteine‐mediated aggregates, nonaggregative cysteine to serine mutants were also generated. The proteins were characterized physicochemically, immunologically, and in in vivo models with or without adjuvant. Results The structurally modified proteins showed significantly decreased IgE binding capacity. Notably, both in vivo models revealed reduced immunogenicity of the hypoallergenic fold variants. When formulated with alum, the monomeric cysteine mutants induced a similar immune response as the aggregated parental allergens, which is in contrast with data published on B et v 1. Conclusion These findings lead to the suggestion that the B et v 1 structure has unique intrinsic properties, which could account for its high allergenicity. Obviously, these characteristics are not entirely shared with its food homologues from apple and hazelnut. Thus, it is important to tackle pollen‐related food allergies from different angles for the generation of effective vaccine candidates to treat birch PFS .