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

Allergy. 2017 Apr;72(4):570-578. doi: 10.1111/all.13041. Epub 2016 Dec 22.

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.

Keywords: allergy model; dendritic cells; immunotherapy; microparticles.

MeSH terms

  • Adjuvants, Immunologic*
  • Allergens / administration & dosage
  • Allergens / immunology*
  • Animals
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Desensitization, Immunologic* / methods
  • Disease Models, Animal
  • Female
  • Hydroxyapatites* / chemistry
  • Hypersensitivity / immunology*
  • Hypersensitivity / therapy
  • Immunization
  • Immunoglobulin E / immunology
  • Immunoglobulin G / immunology
  • Lymphocyte Activation / immunology
  • Mice
  • Ovalbumin / immunology
  • Phosphatidylethanolamines* / chemistry
  • Strontium* / chemistry
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Treatment Outcome

Substances

  • Adjuvants, Immunologic
  • Allergens
  • Hydroxyapatites
  • Immunoglobulin G
  • Phosphatidylethanolamines
  • strontium hydroxyapatite
  • dioleoyl phosphatidylethanolamine
  • Immunoglobulin E
  • Ovalbumin
  • Strontium