期刊
AAPS JOURNAL
卷 16, 期 6, 页码 1185-1193出版社
SPRINGER
DOI: 10.1208/s12248-014-9654-z
关键词
experimental autoimmune encephalomyelitis; multivalency; proteolipid peptide; scaffold; soluble antigen array
资金
- NIH [1R56AI091996-01A1]
- KINBRE [P20 RR016475/P20 GM103418]
- Madison and Lila Self Graduate Fellowship (University of Kansas)
- Institute for Advancing Medical Innovation Graduate Fellowship (University of Kansas)
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 alpha(L)-integrin (CD11a(237-246), 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.
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