Allergen-loaded strontium-doped hydroxyapatite spheres improve allergen-specific immunotherapy in mice

作者：Garbani M; Xia W; Rhyner C; Prati M; Scheynius A; Malissen B; Engqvist H; Maurer M; Crameri R; Terhorst D

来源：Allergy, 2017, 72(4): 570-578.

DOI：10.1111/all.13041

• allergy model
• dendritic cells
• immunotherapy
• microparticles

BackgroundImmunomodulatory 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 resultsScanning 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.
ConclusionWe conclude that SHAS may constitute a suitable carrier and adjuvant for ASIT with great potential due to its unique protein-binding properties.

• 出版日期2017-4