The AAPS Journal

, Volume 16, Issue 6, pp 1185–1193 | Cite as

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

  • Joshua O. Sestak
  • Amir Fakhari
  • Ahmed H. Badawi
  • Teruna J. Siahaan
  • Cory Berkland
Research Article Theme: Nanoparticles in Vaccine Delivery
Part of the following topical collections:
  1. Theme: Nanoparticles in Vaccine Delivery


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.


experimental autoimmune encephalomyelitis multivalency proteolipid peptide scaffold soluble antigen array 



This work was supported by the NIH (1R56AI091996-01A1), KINBRE (P20 RR016475/P20 GM103418), Madison and Lila Self Graduate Fellowship (University of Kansas), and The Institute for Advancing Medical Innovation Graduate Fellowship (University of Kansas).

Supplementary material

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Supplementary Figure 1 (DOCX 1.29 kb)
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Supplementary Figure 2 (DOCX 162 kb)
12248_2014_9654_MOESM3_ESM.docx (104 kb)
Supplementary Figure 3 (DOCX 104 kb)


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Copyright information

© American Association of Pharmaceutical Scientists 2014

Authors and Affiliations

  • Joshua O. Sestak
    • 1
  • Amir Fakhari
    • 3
  • Ahmed H. Badawi
    • 1
  • Teruna J. Siahaan
    • 1
  • Cory Berkland
    • 1
    • 2
    • 3
  1. 1.Department of Pharmaceutical ChemistryUniversity of KansasLawrenceUSA
  2. 2.Department of Chemical and Petroleum EngineeringUniversity of KansasLawrenceUSA
  3. 3.Department of BioengineeringUniversity of KansasLawrenceUSA

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