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Scientific Reports / Conjugation of wildtype and hypoallergenic mugwort allergen Art v 1 to flagellin induces IL-10-DC and suppresses allergen-specific TH2-responses in vivo

Authors :
Schülke, Stefan
Kuttich, Kirsten
Wolfheimer, Sonja
Duschek, Nadine
Wangorsch, Andrea
Reuter, Andreas
Briza, Peter
Pablos, Isabel
Gadermaier, Gabriele
Ferreira, Fatima
Vieths, Stefan
Toda, Masako
Scheurer, Stephan
Publication Year :
2017
Publisher :
Nature Research, 2017.

Abstract

Allergies to weed pollen including members of the Compositae family, such as mugwort, ragweed, and feverfew are spreading worldwide. To efficiently treat these newly arising allergies, allergen specific immunotherapy needs to be improved. Therefore, we generated novel vaccine candidates consisting of the TLR5-ligand Flagellin A from Listeria and the major mugwort allergen Art v 1 including either the wild type Art v 1 sequence (rFlaA:Artv1) or a hypoallergenic variant (rFlaA:Artv1hyp) with reduced IgE-binding capacity. Immune modulating capacity of these constructs and respective controls was evaluated in vitro and in vivo. Incorporation of hypoallergenic Art v 1 derivative did not interfere with the resulting fusion proteins immune stimulatory capacity. Both rFlaA:Artv1 and rFlaA:Artv1hyp induced a prominent, mTOR-dependent, IL-10 secretion from murine dendritic cells, and suppressed allergen-specific TH2-cytokine secretion in vitro and in vivo. Both conjugates retained the capacity to induce rFlaA-specific antibody responses while efficiently inducing production of Art v 1-specific IgG1 and IgG2a antibodies in mice. Interestingly, only the suppression of TH2-cytokine secretion by rFlaA:Artv1 (but not rFlaA:Artv1hyp) was paralleled by a strong secretion of IFN-. In summary, we provided evidence that incorporating hypoallergens into flagellin:allergen fusion proteins is a suitable strategy to further improve these promising vaccine candidates. (VLID)3865626

Details

Language :
English
Database :
OpenAIRE
Accession number :
edsair.od......3941..f04aecaded365d29e1f34032c28e7fcd
Full Text :
https://doi.org/10.1038/s41598-017-11972-w