Hypoallergenic derivatives of Fel d 1 obtained by rational reassembly for allergy vaccination and tolerance induction

• DOI: 10.1111/cea.12294
• Publication Date: 2014-02-19T21:40:03Z
• Authors: M. Curin; M. Weber; T. Thalhamer; I. Swoboda; M. Focke‐Tejkl; K. Blatt; P. Valent; K. Marth; T. Garmatiuk; H. Grönlund; J. Thalhamer; S. Spitzauer; R. Valenta
• Keywords: Hypoallergenic

The major cat allergen Fel d 1 represents one of the most important respiratory allergens. Aim this study was to engineer recombinant derivatives with reduced IgE reactivity and preserved T cell epitopes for vaccination tolerance induction.Seven mosaic proteins were generated by reassembly non-IgE-reactive peptides which contained sequence elements induction allergen-specific blocking IgG antibodies epitopes. Mosaic expressed in Escherichia coli using codon-optimized synthetic genes compared regarding structural fold circular dichroism, IgE-binding capacity, activation allergic patients' basophils ability induce upon immunization.Although each had lost alpha-helical typical 1, a strong reduction as well allergenic activity basophil assays only obtained three constructs, two reassembled fragments (Fel MB, MC) fusion latter MF) cysteines MC replaced serines. Immunization rabbits MF induced high levels that inhibited cat-allergic patients comparable manner wild-type allergen.We report development hypoallergenic suitable patients.