A combination dual-sized microparticle system modulates dendritic cells and prevents type 1 diabetes in prediabetic NOD mice

Abstract We developed a novel poly(lactic-co-glycolic acid)-based, microparticle (MP) system providing concurrent delivery of multiple encapsulated immuno-suppressive factors and antigen, for in vivo conditioning of dendritic cells (DCs) toward a tolerance promoting pathway. Subcutaneous administrat...

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Bibliographic Details
Published in:Clinical immunology (Orlando, Fla.) Fla.), 2015-09, Vol.160 (1), p.90-102
Main Authors: Lewis, Jamal S, Dolgova, Natalia V, Zhang, Ying, Xia, Chang Qing, Wasserfall, Clive H, Atkinson, Mark A, Clare-Salzler, Michael J, Keselowsky, Benjamin G
Format: Article
Language:English
Subjects:
Allergy and Immunology
Animals
CD4-Positive T-Lymphocytes - immunology
Cells, Cultured
Cholecalciferol - pharmacology
Dendritic cells
Dendritic Cells - immunology
Diabetes
Diabetes Mellitus, Type 1 - prevention & control
Drug Carriers
Female
Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology
Immune Tolerance - immunology
Insulin - pharmacology
Lactic Acid
Lipopolysaccharides
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred NOD
Microparticle
NOD
Particle Size
Peptide Fragments - pharmacology
Polyglycolic Acid
Prevention
Tolerance
Transforming Growth Factor beta1 - pharmacology
Vaccines - administration & dosage
Vaccines - immunology
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Summary:Abstract We developed a novel poly(lactic-co-glycolic acid)-based, microparticle (MP) system providing concurrent delivery of multiple encapsulated immuno-suppressive factors and antigen, for in vivo conditioning of dendritic cells (DCs) toward a tolerance promoting pathway. Subcutaneous administration prevents onset of type 1 diabetes (T1D) in NOD mice. Two MP sizes were made: phagocytosable MPs were fabricated encapsulating vitamin D3 or insulin B(9–23) peptide, while unphagocytosable MPs were fabricated encapsulating TGF-β1 or GM-CSF. The combination of Vit D3/TGF-β1 MPs confers an immature and LPS activation-resistant phenotype to DCs, and MP-delivered antigen is efficiently and functionally presented. Notably, two subcutaneous injections into 4 week old NOD mice using the combination of MPs encapsulating Vit D3, Ins B, TGF-β1 and GM-CSF protected 40% of mice from T1D development, significant in comparison to the control. This work represents one of the first applications of a biomaterial-based, MP vaccine system to successfully prevent autoimmune diabetes.
ISSN:1521-6616
1521-7035
DOI:10.1016/j.clim.2015.03.023