Allergens displayed on virus-like particles are highly immunogenic but fail to activate human mast cells.
<h4>Background</h4> <p>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 (VL...
| প্রধান লেখক: | , , , , , |
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| বিন্যাস: | Journal article |
| ভাষা: | English |
| প্রকাশিত: |
Wiley
2017
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| _version_ | 1826298874223919104 |
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| author | Engeroff, P Caviezel, F Storni, F Thoms, F Vogel, M Bachmann, MF |
| author_facet | Engeroff, P Caviezel, F Storni, F Thoms, F Vogel, M Bachmann, MF |
| author_sort | Engeroff, P |
| collection | OXFORD |
| description | <h4>Background</h4> <p>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.</p> <h4>Methods</h4> <p>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.</p> <h4>Results</h4> <p>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.</p> <h4>Conclusion</h4> <p>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.</p> |
| first_indexed | 2024-03-07T04:53:25Z |
| format | Journal article |
| id | oxford-uuid:d5c1c98e-3fb6-45e8-94f2-396549d4cc2a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:53:25Z |
| publishDate | 2017 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:d5c1c98e-3fb6-45e8-94f2-396549d4cc2a2022-03-27T08:28:21ZAllergens displayed on virus-like particles are highly immunogenic but fail to activate human mast cells.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d5c1c98e-3fb6-45e8-94f2-396549d4cc2aEnglishSymplectic Elements at OxfordWiley2017Engeroff, PCaviezel, FStorni, FThoms, FVogel, MBachmann, MF <h4>Background</h4> <p>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.</p> <h4>Methods</h4> <p>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.</p> <h4>Results</h4> <p>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.</p> <h4>Conclusion</h4> <p>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.</p> |
| spellingShingle | Engeroff, P Caviezel, F Storni, F Thoms, F Vogel, M Bachmann, MF Allergens displayed on virus-like particles are highly immunogenic but fail to activate human mast cells. |
| title | Allergens displayed on virus-like particles are highly immunogenic but fail to activate human mast cells. |
| title_full | Allergens displayed on virus-like particles are highly immunogenic but fail to activate human mast cells. |
| title_fullStr | Allergens displayed on virus-like particles are highly immunogenic but fail to activate human mast cells. |
| title_full_unstemmed | Allergens displayed on virus-like particles are highly immunogenic but fail to activate human mast cells. |
| title_short | Allergens displayed on virus-like particles are highly immunogenic but fail to activate human mast cells. |
| title_sort | allergens displayed on virus like particles are highly immunogenic but fail to activate human mast cells |
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