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Allergens displayed on virus‐like particles are highly immunogenic but fail to activate human mast cells
Author(s) -
Engeroff P.,
Caviezel F.,
Storni F.,
Thoms F.,
Vogel M.,
Bachmann M. F.
Publication year - 2018
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.13268
Subject(s) - mast (botany) , immunology , virus , mast cell , virology , allergy , biology , medicine
Background The goal of allergen‐specific immunotherapy is the induction of protective immune responses in the absence of anaphylactic reactions. We have previously shown that Fel d 1, the major cat allergen, displayed in a repetitive fashion on virus‐like particles ( VLP s) may fulfill these criteria. Specifically, Fel d 1 on VLP s induced strongly increased protective IgG responses compared to free allergen in mice while anaphylactic reactions were essentially abolished. Here we extend these findings to human mast cells and offer a mechanistic explanation for the reduced anaphylactic activity. Methods We differentiated human mast cells in vitro from blood‐derived stem cell progenitors and sensitized the cells with a monoclonal Fel d 1‐specific IgE. We compared the capability of Fel d 1 to induce mast cell activation in its free form versus displayed on VLP s and we performed allergen binding studies by surface plasmon resonance as well as flow cytometry. Results We show that free Fel d 1 induces degranulation of IgE‐sensitized mast cells whereas Fel d 1 displayed on VLP s fails to induce mast cell activation. We demonstrate that this inability to activate mast cells is based on a biophysical as well as a biochemical mechanism. Firstly, Fel d 1 on VLP s showed a strongly impaired ability to bind to surface‐bound IgE. Secondly, despite residual binding, repetitively displayed allergen on VLP s failed to cause mast cell activation. Conclusion These findings indicate that repetitively displaying allergens on VLP s increases their immunogenicity while reducing their potential to cause anaphylactic reactions by essentially eliminating IgE‐mediated activation of mast cells.