Allergens displayed on virus-like particles are highly immunogenic but fail to activate human mast cells.
Allergy
; 73(2): 341-349, 2018 02.
Article
in En
| MEDLINE
| ID: mdl-28787769
ABSTRACT
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 (VLPs) may fulfill these criteria. Specifically, Fel d 1 on VLPs 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 VLPs 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 VLPs 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 VLPs showed a strongly impaired ability to bind to surface-bound IgE. Secondly, despite residual binding, repetitively displayed allergen on VLPs failed to cause mast cell activation.CONCLUSION:
These findings indicate that repetitively displaying allergens on VLPs increases their immunogenicity while reducing their potential to cause anaphylactic reactions by essentially eliminating IgE-mediated activation of mast cells.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Allergens
/
Vaccines, Virus-Like Particle
/
Mast Cells
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Allergy
Year:
2018
Document type:
Article
Affiliation country:
Switzerland