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

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.
Competing Interests: Competing interestsM.P. is the inventor of “Cytokine Signaling Immunomodulators and Methods”, and “fentanyl hapten-conjugates and methods for making and using same” patents. The anti-IL-13 mAb was obtained from Genentech under a standard Material Transfer Agreement. All authors declare that there are no other competing interests.
(© The Author(s) 2020.)