Co-delivery of autoantigen and dexamethasone in incomplete Freund's adjuvant ameliorates experimental autoimmune encephalomyelitis

Abstract

Current therapies for autoimmune diseases focus on treating the symptoms rather than the underlying disease cause. A major setback in improving current therapeutics for autoimmunity is the lack of antigen specificity. Successful antigen-specific immunotherapy (ASIT) would allow for improved treatment of autoimmune diseases. In this work, dexamethasone was co-delivered with autoantigen (PLP) in vivo to create effective ASIT for the treatment of experimental autoimmune encephalomyelitis (EAE). Using an emulsion of incomplete Freund’s adjuvant (IFA) as a co-delivery vehicle, it was discovered that the controlled release of autoantigen was important for the suppression of clinical disease symptoms. Analysis of the immune response via cytokines revealed that dexamethasone was important for shifting the immune response away from inflammation. Co-delivery of both autoantigen and dexamethasone increased B-cell populations and antibody production, signifying an increased humoral immune response. Overall, this data indicated that the co-delivery of PLP and dexamethasone with a water-in-oil emulsion is effective in treating a murine autoimmune model.

Tocopherol Emulsions as Functional Autoantigen Delivery Vehicles Evoke Therapeutic Efficacy in Experimental Autoimmune Encephalomyelitis

“…6A–D). In a previous study, therapeutic success was achieved when delivering PLP and dexamethasone with IFA, and differences in a distinct population of CD19+CD11c+ were seen [23]. These differences were believed to be mechanistically contributive, though in this work, no population differences in this subtype were observed (Fig.…”

“…Mouse spleens were harvested from EAE mice on day 25 post-immunization as previously described [23, 45, 46]. Briefly, the spleens were first passed through a wire mesh using the rubber end of a sterile 1 mL syringe plunger and collected in 5 mL of RPMI 1640 media.…”

Antigen-Specific Immune Decoys Intercept and Exhaust Autoimmunity to Prevent Disease

“…Induction of EAE and Therapeutic Study. EAE was induced as previously described [47,59] Detection of Anti-PLP IgG. PLP-specific IgG titers were assessed in an ELISA format as previously described [47,48].…”

Soluble antigen arrays disarm antigen-specific B cells to promote lasting immune tolerance in experimental autoimmune encephalomyelitis

“…Secreted cytokines (IL-4, IL-10, IL-6, GM-CSF, IL-2, IFN-γ, IL-17, IL-15, IL-23, and TNF-α) were detected using a U-Plex Mouse Biomarker Group 1 Multiplex Assay ELISA kit (Meso Scale Discovery (MSD), Rockville, MD) according to manufacturer guidelines, as previously described. 31…”