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


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.

SUBMITTER: Crouse B 

PROVIDER: S-EPMC7578047 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Crouse Bethany B   Robinson Christine C   Huseby Kelcher April A   Laudenbach Megan M   Abrahante Juan E JE   Pravetoni Marco M  

NPJ vaccines 20201021


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  ...[more]

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