title: Co-delivery of autoantigen and b7 pathway modulators suppresses experimental autoimmune encephalomyelitis.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas, 2030 Becker Drive, 320E, Lawrence, Kansas, 66047, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Northrup
authors.forename: Joshua O
authors.initials: JO
authors.lastname: Sestak
authors.forename: Bradley P
authors.initials: BP
authors.lastname: Sullivan
authors.forename: Sharadvi
authors.initials: S
authors.lastname: Thati
authors.forename: Brittany L
authors.initials: BL
authors.lastname: Hartwell
authors.forename: Teruna J
authors.initials: TJ
authors.lastname: Siahaan
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Vines
authors.forename: Cory
authors.initials: C
authors.lastname: Berkland
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D060887:B7 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004337:Drug Carriers / Q000737:chemistry*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D006820:Hyaluronic Acid / Q000737:chemistry; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology; D008815:Mice, Inbred Strains; D018991:Myelin Proteolipid Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D012995:Solubility; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology
chemical_list: D001324:Autoantigens; D060887:B7 Antigens; D016207:Cytokines; D004337:Drug Carriers; D018991:Myelin Proteolipid Protein; C573814:PLP-BPI peptide; D010446:Peptide Fragments; D010455:Peptides; C435023:myelin proteolipid protein (139-151); D006820:Hyaluronic Acid