Co-Delivery of Autoantigen and B7 Pathway Modulators Suppresses Experimental Autoimmune Encephalomyelitis

Autoimmune diseases such as multiple sclerosis (MS) are characterized by the breakdown of immune tolerance to autoantigens. Targeting surface receptors on immune cells offers a unique strategy for reprogramming immune responses in autoimmune diseases. The B7 signaling pathway was targeted using adap...

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Bibliographic Details
Published in:The AAPS journal 2014-11, Vol.16 (6), p.1204-1213
Main Authors: Northrup, Laura, Sestak, Joshua O., Sullivan, Bradley P., Thati, Sharadvi, Hartwell, Brittany L., Siahaan, Teruna J., Vines, Charlotte M., Berkland, Cory
Format: Article
Language:English
Subjects:
Animals
Autoantigens - immunology
B7 Antigens - immunology
Biochemistry
Biomedical and Life Sciences
Biomedicine
Biotechnology
Cells, Cultured
Cytokines - biosynthesis
Cytokines - immunology
Drug Carriers - chemistry
Encephalomyelitis, Autoimmune, Experimental - drug therapy
Encephalomyelitis, Autoimmune, Experimental - immunology
Female
Hyaluronic Acid - chemistry
Immune Tolerance - drug effects
Immune Tolerance - immunology
Mice, Inbred Strains
Myelin Proteolipid Protein - immunology
Peptide Fragments - immunology
Peptides - administration & dosage
Peptides - chemistry
Peptides - therapeutic use
Pharmacology/Toxicology
Pharmacy
Research Article
Solubility
Spleen - cytology
Spleen - drug effects
Spleen - immunology
Theme: Nanoparticles in Vaccine Delivery
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Summary:Autoimmune diseases such as multiple sclerosis (MS) are characterized by the breakdown of immune tolerance to autoantigens. Targeting surface receptors on immune cells offers a unique strategy for reprogramming immune responses in autoimmune diseases. The B7 signaling pathway was targeted using adaptations of soluble antigen array (SAgA) technology achieved by covalently linking B7-binding peptides and disease causing autoantigen (proteolipid peptide (PLP)) to hyaluronic acid (HA). We hypothesized that co-delivery of a B7-binding peptide and autoantigen would suppress experimental autoimmune encephalomyelitis (EAE), a murine model of MS. Three independent B7-targeted SAgAs were created containing peptides to either inhibit or potentially stimulate the B7 signaling pathway. Surprisingly, all SAgAs were found to suppress EAE disease symptoms. Altered cytokine expression was observed in primary splenocytes isolated from SAgA-treated mice, indicating that SAgAs with different B7-binding peptides may suppress EAE through different immunological mechanisms. This antigen-specific immunotherapy using SAgAs can successfully suppress EAE through co-delivery of autoantigen and peptides targeting with the B7 signaling pathway.
ISSN:1550-7416
1550-7416
DOI:10.1208/s12248-014-9671-y