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

Laura Northrup, J. Daniel Griffin, Matthew A. Christopher, Lorena R. Antunez, Brittany L. Hartwell, Chad J. Pickens, Cory Berkland

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)156-165
Number of pages10
JournalJournal of Controlled Release
Volume266
DOIs
StatePublished - Nov 28 2017
Externally publishedYes

Bibliographical note

Funding Information:
LN was supported by the American Association of Pharmaceutical Scientists (AAPS) Foundation Graduate Fellowship. JDG and BLH were supported by the Madison and Lila Self Graduate Fellowship at the University of Kansas. MAC was supported by the Biotechnology Predoctoral Training Program ( T32-GM008359 ) at the University of Kansas . CJP was supported by NIH training grant T32 GM008545 and the Howard Rytting pre-doctoral fellowship from the Department of Pharmaceutical Chemistry at the University of Kansas. The authors would like to acknowledge the Kansas Vaccine Institute at the University of Kansas, specifically Francisco J. Martinez-Becerra, for his assistance with flow cytometry, ELISpot, and cytokine measurements with MSD Multiplex. Additionally, the authors thank Joseph St.Amand for his assistance with data analysis to determine trends. Lastly, the authors thank Heather Shinogle of the Microscopy and Analytical Imaging Core Laboratory at the University of Kansas for her assistance in collecting and analyzing IFA emulsion images.

Publisher Copyright:
© 2017 Elsevier B.V.

Keywords

  • Antigen-specific immunotherapy
  • Co-delivery
  • Dexamethasone
  • Experimental autoimmune encephalomyelitis (EAE)
  • Incomplete Freund's adjuvant (IFA)
  • Proteolipid protein (PLP)

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