PMID- 27590538 OWN - NLM STAT- MEDLINE DCOM- 20171207 LR - 20171207 IS - 1398-9995 (Electronic) IS - 0105-4538 (Linking) VI - 72 IP - 4 DP - 2017 Apr TI - Allergen-loaded strontium-doped hydroxyapatite spheres improve allergen-specific immunotherapy in mice. PG - 570-578 LID - 10.1111/all.13041 [doi] AB - 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. CI - (c) 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Garbani, M AU - Garbani M AD - Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos Platz, Switzerland. FAU - Xia, W AU - Xia W AD - Applied Materials Science, Department of Engineering Sciences, Angstrom Laboratory, Uppsala University, Uppsala, Sweden. FAU - Rhyner, C AU - Rhyner C AD - Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos Platz, Switzerland. FAU - Prati, M AU - Prati M AD - Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos Platz, Switzerland. FAU - Scheynius, A AU - Scheynius A AD - Department of Clinical Science and Education, Karolinska Institutet, and Sachs' Children and Youth Hospital, Sodersjukhuset, Stockholm, Sweden. FAU - Malissen, B AU - Malissen B AD - Centre d'Immunologie de Marseille-Luminy (CIML), INSERM U1104, CNRS UMR7280, UM2 Aix-Marseille Universite, Marseille Cedex 9, France. FAU - Engqvist, H AU - Engqvist H AD - Applied Materials Science, Department of Engineering Sciences, Angstrom Laboratory, Uppsala University, Uppsala, Sweden. FAU - Maurer, M AU - Maurer M AD - Department of Dermatology and Allergy, Allergie-Centrum-Charite, Charite -Universitatsmedizin Berlin, Berlin, Germany. FAU - Crameri, R AU - Crameri R AD - Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos Platz, Switzerland. FAU - Terhorst, D AU - Terhorst D AD - Centre d'Immunologie de Marseille-Luminy (CIML), INSERM U1104, CNRS UMR7280, UM2 Aix-Marseille Universite, Marseille Cedex 9, France. AD - Department of Dermatology and Allergy, Allergie-Centrum-Charite, Charite -Universitatsmedizin Berlin, Berlin, Germany. AD - Berlin Institute of Health (BIH), Berlin, Germany. LA - eng PT - Journal Article DEP - 20161222 PL - Denmark TA - Allergy JT - Allergy JID - 7804028 RN - 0 (Adjuvants, Immunologic) RN - 0 (Allergens) RN - 0 (Hydroxyapatites) RN - 0 (Immunoglobulin G) RN - 0 (Phosphatidylethanolamines) RN - 0 (strontium hydroxyapatite) RN - 2462-63-7 (dioleoyl phosphatidylethanolamine) RN - 37341-29-0 (Immunoglobulin E) RN - 9006-59-1 (Ovalbumin) RN - YZS2RPE8LE (Strontium) SB - IM MH - *Adjuvants, Immunologic MH - Allergens/administration & dosage/*immunology MH - Animals MH - Dendritic Cells/immunology/metabolism MH - *Desensitization, Immunologic/methods MH - Disease Models, Animal MH - Female MH - *Hydroxyapatites/chemistry MH - Hypersensitivity/*immunology/therapy MH - Immunization MH - Immunoglobulin E/immunology MH - Immunoglobulin G/immunology MH - Lymphocyte Activation/immunology MH - Mice MH - Ovalbumin/immunology MH - *Phosphatidylethanolamines/chemistry MH - *Strontium/chemistry MH - T-Lymphocyte Subsets/immunology/metabolism MH - Treatment Outcome OTO - NOTNLM OT - allergy model OT - dendritic cells OT - immunotherapy OT - microparticles EDAT- 2016/09/04 06:00 MHDA- 2017/12/08 06:00 CRDT- 2016/09/04 06:00 PHST- 2016/09/01 00:00 [accepted] PHST- 2016/09/04 06:00 [pubmed] PHST- 2017/12/08 06:00 [medline] PHST- 2016/09/04 06:00 [entrez] AID - 10.1111/all.13041 [doi] PST - ppublish SO - Allergy. 2017 Apr;72(4):570-578. doi: 10.1111/all.13041. Epub 2016 Dec 22.