title: Structure, size, and solubility of antigen arrays determines efficacy in experimental autoimmune encephalomyelitis.
abstract: Presentation of antigen with immune stimulating "signal" has been a cornerstone of vaccine design for decades. Here, the antigen plus immune "signal" of vaccines is modified to produce antigen-specific immunotherapies (antigen-SITs) that can potentially reprogram the immune response toward tolerance of an autoantigen. The codelivery of antigen with a cell adhesion inhibitor using Soluble Antigen Arrays (SAgAs) was previously shown to slow or halt experimental autoimmune encephalomyelitis (EAE), a murine form of multiple sclerosis (MS). SAgAs are comprised of a hyaluronic acid backbone with cografted intercellular cell adhesion molecule-1 ligand derived from αL-integrin (CD11a237-246, "LABL") and an encephalitogenic epitope peptide of proteolipid protein (PLP139-151, "PLP"). Here, the physical characteristics of the carrier were investigated to evaluate how structure, size, and solubility drive the immune response when treating EAE. A bifunctional peptide (small, soluble), SAgAs (large, soluble), and PLGA nanoparticles (large, insoluble) all displaying PLP and LABL in equimolar ratios were compared. Maximum EAE suppression was achieved with coincident display of both peptides on a soluble construct.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas, 2030 Becker Dr., Lawrence, Kansas, 66047, USA.
authors.forename: Joshua O
authors.initials: JO
authors.lastname: Sestak
authors.forename: Amir
authors.initials: A
authors.lastname: Fakhari
authors.forename: Ahmed H
authors.initials: AH
authors.lastname: Badawi
authors.forename: Teruna J
authors.initials: TJ
authors.lastname: Siahaan
authors.forename: Cory
authors.initials: C
authors.lastname: Berkland
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D040881:CD11a Antigen / Q000276:immunology; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D006820:Hyaluronic Acid / Q000737:chemistry; D007108:Immune Tolerance / Q000187:drug effects*; D019344:Lactic Acid / Q000737:chemistry; D008815:Mice, Inbred Strains; D018991:Myelin Proteolipid Protein / Q000276:immunology; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D010446:Peptide Fragments / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility
chemical_list: D001324:Autoantigens; D040881:CD11a Antigen; D004337:Drug Carriers; D018991:Myelin Proteolipid Protein; C573814:PLP-BPI peptide; D010446:Peptide Fragments; D010455:Peptides; C435023:myelin proteolipid protein (139-151); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006820:Hyaluronic Acid