Opioid use disorders (OUD) affect over 27 million people worldwide. Anti-opioid vaccines offer a promising strategy to treat OUD and prevent overdose. Using immunomodulation of cytokine signaling to increase vaccine efficacy, this study found that blocking IL-4 improved the efficacy of vaccines targeting oxycodone and fentanyl in male and female mice. Genetic deletion of the IL-4 receptor, STAT6, or antibody-based depletion of IL-13, did not increase vaccine efficacy against opioids, suggesting the involvement of type I IL-4 receptors. Enhancement of vaccine efficacy with blockade of IL-4 was associated with improved germinal center formation in secondary lymphoid organs and selective transcriptome signatures in the activated CD4+ T cell population subset. These data suggest that IL-4 is both a pharmacological target and a potential biomarker of vaccine efficacy against OUD.
|Original language||English (US)|
|State||Published - Dec 1 2020|
Bibliographical noteFunding Information:
This work was supported by DA041730 (M.P.), T32DA007097 (B.C.), and T32DA037183 (A.H.K.). The authors thank the following University of Minnesota core facilities for technical and research support: University Imaging Center, University Flow Cytometry Resource, the Genomics Center, and the Informatics Institute. The authors thank Drs. Stephen Jameson and Kris Hogquist at the University of Minnesota Center for Immunology for providing NKT cell reagents.
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