Skip to Content
Merck
  • 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 encephalomyelitis.

The AAPS journal (2014-09-07)
Joshua O Sestak, Amir Fakhari, Ahmed H Badawi, Teruna J Siahaan, Cory Berkland
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Acetonitrile solution, contains 10.0% acetone, 0.05% formic acid, 40.0% 2-propanol
Sigma-Aldrich
Acetonitrile solution, contains 0.05 % (w/v) ammonium formate, 5 % (v/v) water, 0.1 % (v/v) formic acid, suitable for HPLC
Supelco
Mannitol, Pharmaceutical Secondary Standard; Certified Reference Material
Mannitol, European Pharmacopoeia (EP) Reference Standard
Supelco
Acetone, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Mannitol, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Acetic acid-12C2, 99.9 atom % 12C
Supelco
D-Mannitol, ≥99.9999% (metals basis), for boron determination
Sigma-Aldrich
Acetonitrile solution, contains 0.1 % (v/v) formic acid, suitable for HPLC
Sigma-Aldrich
Acetone, suitable for HPLC, ≥99.9%
Sigma-Aldrich
Acetonitrile solution, contains 0.05 % (v/v) trifluoroacetic acid
Sigma-Aldrich
Acetone, natural, ≥97%
Sigma-Aldrich
Acetonitrile solution, contains 0.1 % (v/v) trifluoroacetic acid, suitable for HPLC
Sigma-Aldrich
tert-Butyl carbazate, 98%
Sigma-Aldrich
Diethyl ether, puriss. p.a., ACS reagent, ≥99.8% (GC)
Sigma-Aldrich
Sodium acetate, 99.995% trace metals basis
Supelco
Acetic acid, analytical standard
Supelco
Diethyl ether, analytical standard
Supelco
Acetone, analytical standard
Sigma-Aldrich
Sodium acetate, anhydrous, BioUltra, for luminescence, for molecular biology, ≥99.0% (NT)
Sigma-Aldrich
Sodium acetate solution, BioUltra, for molecular biology, ~3 M in H2O
Sigma-Aldrich
D-Mannitol, tested according to Ph. Eur.
Sigma-Aldrich
Sodium Acetate Anhydrous, >99%, FG
Sigma-Aldrich
D-Mannitol, BioUltra, ≥99.0% (sum of enantiomers, HPLC)
Sigma-Aldrich
Acetic acid, ≥99.5%, FCC, FG
Sigma-Aldrich
Diethyl ether, contains 1 ppm BHT as inhibitor, anhydrous, ≥99.7%
Sigma-Aldrich
Acetone, ≥99%, meets FCC analytical specifications
Millipore
D-Mannitol, ACS reagent, ≥99.0%, suitable for microbiology
Sigma-Aldrich
Sodium acetate, BioXtra, ≥99.0%
Sigma-Aldrich
Sodium acetate, meets USP testing specifications, anhydrous