Mechanisms of interleukin 4 mediated increase in efficacy of vaccines against opioid use disorders

Bethany Crouse; Christine Robinson; April Huseby Kelcher; Megan Laudenbach; Juan E Abrahante; Marco Pravetoni

doi:10.1038/s41541-020-00247-7

Mechanisms of interleukin 4 mediated increase in efficacy of vaccines against opioid use disorders

NPJ Vaccines. 2020 Oct 21:5:99. doi: 10.1038/s41541-020-00247-7. eCollection 2020.

Authors

Bethany Crouse^{1

2}, Christine Robinson¹, April Huseby Kelcher^{1

3}, Megan Laudenbach⁴, Juan E Abrahante⁵, Marco Pravetoni^{1

6}

Affiliations

¹ Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455 USA.
² Department of Veterinary Population Medicine, University of Minnesota, St. Paul, MN 55455 USA.
³ Department of Psychiatry and Behavioral Sciences, University of Minnesota Medical School, Minneapolis, MN 55455 USA.
⁴ Hennepin Healthcare Research Institute, Minneapolis, MN 55404 USA.
⁵ University of Minnesota Informatics Institute, Minneapolis, MN 55455 USA.
⁶ Center for Immunology, University of Minnesota, Minneapolis, MN 55455 USA.

Abstract

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.

Keywords: Addiction; Adjuvants; Conjugate vaccines.

Abstract

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