Header

UZH-Logo

Maintenance Infos

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


Garbani, M; Xia, W; Rhyner, C; Prati, M; Scheynius, A; Malissen, B; Engqvist, H; Maurer, M; Crameri, R; Terhorst, D (2017). Allergen-loaded strontium-doped hydroxyapatite spheres improve allergen-specific immunotherapy in mice. Allergy, 72(4):570-578.

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. SHAS 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. ASIT 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.

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. SHAS 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. ASIT 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.

Statistics

Citations

4 citations in Web of Science®
1 citation in Scopus®
Google Scholar™

Altmetrics

Downloads

10 downloads since deposited on 06 Dec 2016
10 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Swiss Institute of Allergy and Asthma Research
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2017
Deposited On:06 Dec 2016 07:47
Last Modified:08 Dec 2017 21:04
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:0105-4538
Publisher DOI:https://doi.org/10.1111/all.13041
PubMed ID:27590538

Download

Download PDF  'Allergen-loaded strontium-doped hydroxyapatite spheres improve allergen-specific immunotherapy in mice'.
Preview
Content: Accepted Version
Filetype: PDF
Size: 810kB
View at publisher