title: Allergen-loaded strontium-doped hydroxyapatite spheres improve allergen-specific immunotherapy in mice.
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).
  
  
  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.
  
  
  CONCLUSIONS
  We conclude that SHAS may constitute a suitable carrier and adjuvant for ASIT with great potential due to its unique protein-binding properties.
authors: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos Platz, Switzerland.
authors: M
authors: M
authors: Garbani
authors: Applied Materials Science, Department of Engineering Sciences, Ångström Laboratory, Uppsala University, Uppsala, Sweden.
authors: W
authors: W
authors: Xia
authors: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos Platz, Switzerland.
authors: C
authors: C
authors: Rhyner
authors: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos Platz, Switzerland.
authors: M
authors: M
authors: Prati
authors: Department of Clinical Science and Education, Karolinska Institutet, and Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden.
authors: A
authors: A
authors: Scheynius
authors: Centre d'Immunologie de Marseille-Luminy (CIML), INSERM U1104, CNRS UMR7280, UM2 Aix-Marseille Université, Marseille Cedex 9, France.
authors: B
authors: B
authors: Malissen
authors: Applied Materials Science, Department of Engineering Sciences, Ångström Laboratory, Uppsala University, Uppsala, Sweden.
authors: H
authors: H
authors: Engqvist
authors: Department of Dermatology and Allergy, Allergie-Centrum-Charité, Charité -Universitätsmedizin Berlin, Berlin, Germany.
authors: M
authors: M
authors: Maurer
authors: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos Platz, Switzerland.
authors: R
authors: R
authors: Crameri
authors: Centre d'Immunologie de Marseille-Luminy (CIML), INSERM U1104, CNRS UMR7280, UM2 Aix-Marseille Université, Marseille Cedex 9, France.|Department of Dermatology and Allergy, Allergie-Centrum-Charité, Charité -Universitätsmedizin Berlin, Berlin, Germany.|Berlin Institute of Health (BIH), Berlin, Germany.
authors: D
authors: D
authors: Terhorst
mesh_terms: D000276:Adjuvants, Immunologic; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D003888:Desensitization, Immunologic / Q000379:methods; D004195:Disease Models, Animal; D005260:Female; D006882:Hydroxyapatites / Q000737:chemistry; D006967:Hypersensitivity / Q000276:immunology* / Q000628:therapy; D007114:Immunization; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D010714:Phosphatidylethanolamines / Q000737:chemistry; D013324:Strontium / Q000737:chemistry; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000485:Allergens; D006882:Hydroxyapatites; D007074:Immunoglobulin G; D010714:Phosphatidylethanolamines; C076185:strontium hydroxyapatite; C094877:dioleoyl phosphatidylethanolamine; D007073:Immunoglobulin E; D010047:Ovalbumin; D013324:Strontium
keywords: allergy model; dendritic cells; immunotherapy; microparticles