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Structure, Size, and Solubility of Antigen Arrays Determines Efficacy in Experimental Autoimmune Encephalomyelitis

Structure, Size, and Solubility of Antigen Arrays Determines Efficacy in Experimental Autoimmune... ABSTRACTPresentation 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png "The AAPS Journal" Springer Journals

Structure, Size, and Solubility of Antigen Arrays Determines Efficacy in Experimental Autoimmune Encephalomyelitis

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Publisher
Springer Journals
Copyright
Copyright © American Association of Pharmaceutical Scientists 2014
eISSN
1550-7416
DOI
10.1208/s12248-014-9654-z
Publisher site
See Article on Publisher Site

Abstract

ABSTRACTPresentation 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.

Journal

"The AAPS Journal"Springer Journals

Published: Nov 6, 2014

References