Title | Allergen-loaded strontium-doped hydroxyapatite spheres improve allergen-specific immunotherapy in mice. |
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Authors | Garbani, M.; Xia, W.; Rhyner, C.; Prati, M.; Scheynius, A.; Malissen, B.; Engqvist, H.; Maurer, M.; Crameri, R.; Terhorst, D. |
Journal | Allergy |
DOI | 10.1111/all.13041 |
Abstract |
BACKGROUND: Immunomodulatory interventions play a key role in the treatment of infections and cancer as well as allergic diseases. Adjuvants such as micro- and nanoparticles are often added to immunomodulatory therapies to enhance the triggered immune response. Here, we report the immunological assessment of novel and economically manufactured microparticle adjuvants, namely strontium-doped hydroxyapatite porous spheres (SHAS), which we suggest for the use as adjuvant and carrier in allergen-specific immunotherapy (ASIT). METHODS AND RESULTS: Scanning electron microscopy revealed that the synthesis procedure developed for the production of SHAS results in a highly homogeneous population of spheres. Strontium-doped hydroxyapatite porous spheres bound and released proteins such as ovalbumin (OVA) or the major cat allergen Fel d 1. SHAS-OVA were taken up by human monocyte-derived dendritic cells (mdDCs) and murine DCs and did not have any necrotic or apoptotic effects even at high densities. In a murine model of ASIT for allergic asthmatic inflammation, we found that OVA released from subcutaneously injected SHAS-OVA led to a sustained stimulation of both CD4(+) and CD8(+) T cells. Allergen-specific immunotherapy with SHAS-OVA as compared to soluble OVA resulted in similar humoral responses but in a higher efficacy as assessed by symptom scoring. CONCLUSION: We conclude that SHAS may constitute a suitable carrier and adjuvant for ASIT with great potential due to its unique protein-binding properties. |
Allergen-loaded strontium-doped hydroxyapatite spheres improve allergen-specific immunotherapy in mice.