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

Abstract

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 α L -integrin (CD11a 237-246 , "LABL") and an encephalitogenic epitope peptide of proteolipid protein (PLP 139-151 , "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.

Soluble Antigen Arrays Displaying Mimotopes Direct the Response of Diabetogenic T Cells

“…cSAgA PLP showed enhanced efficacy when compared to SAgA PLP , possibly due the more stable covalent linkage in cSAgA PLP . 7,[17][18][19][20][21][22][23] While the immune response of MS is distinct from T1D, the mechanism of SAgAs offers a general strategy for the delivery of autoantigens. Here, we tailored SAgA technology as an ASIT for T1D.…”

A Tolerogenic Artificial APC Durably Ameliorates Experimental Autoimmune Encephalomyelitis by Directly and Selectively Modulating Myelin Peptide–Autoreactive CD4+ and CD8+ T Cells

“…Numerous researchers around the world have reported the biomimetic micro-and nanoparticles (MNPs) carrying myelin peptides or proteins along with toxin or regulatory molecules for the treatment of EAE or MS (30,40,41). s.c. prophylactic and therapeutic vaccination with PLGA NPs encapsulating MOG 35-55 peptide and IL-10 ameliorated the MOG-induced EAE in mice (42).…”

“…To fabricate the multivalent TaAPCs, PLGA-MPs TGF-b1 were further cocoupled with the target Ags (MOG 40 TaAPCs) were generated in parallel and followed by threecolor staining. The histograms (Fig.…”

Application of nanomedicine for crossing the blood–brain barrier: Theranostic opportunities in multiple sclerosis

“…They showed that the administration of NP-loaded DC could induce immune tolerance in CD4 þ T-cells and inhibit EAE progression. Similarly, Sestak et al (2014) reported how the physical characteristics of the carrier such as structure, size and solubility can modulate the immune response following treating EAE. They evaluated a bifunctional peptide (small and soluble), Soluble Antigen Arrays (SAgAs) (large and soluble) and PLGA NP (large and insoluble) all exhibiting PLP and intercellular cell adhesion molecule-1 ligand derived from aL-integrin (CD11a 237-246 ).…”