Blocking interleukin-4 enhances efficacy of vaccines for treatment of opioid abuse and prevention of opioid overdose

Megan Laudenbach, Federico Baruffaldi, Christine Robinson, Philipp Carter, Davis Seelig, Carly Baehr, Marco Pravetoni

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Vaccines offer an option to treat heroin and prescription opioid abuse and prevent fatal overdoses. Opioid vaccines elicit antibodies that block opioid distribution to the brain and reduce opioid-induced behavioral effects and toxicity. The major limitation to the translation of addiction vaccines is that efficacy is observed only in subjects achieving optimal drug-specific serum antibody levels. This study tested whether efficacy of a vaccine against oxycodone is increased by immunomodulators targeting key cytokine signaling pathways involved in B and T cell lymphocyte activation. Blockage of IL-4 signaling increased vaccine efficacy in blocking oxycodone distribution to the brain and protection against opioid-induced behavior and toxicity in mice. This strategy generalized to a peptide-protein conjugate immunogen, and a tetanus-diphtheria-pertussis vaccine. These data demonstrate that cytokine-based immunomodulators increase efficacy of vaccines against small molecules, peptides and proteins, and identify IL-4 as a pharmacological target for improving efficacy of next-generation vaccines.

Original languageEnglish (US)
Article number5508
JournalScientific reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

Bibliographical note

Funding Information:
This study was supported by National Institutes of Health (NIH) DA041730 and Minneapolis Medical Research Foundation Translational Research Award to M.P. Research reported in this publication was supported by the NIH under Award Number T32DA007097 to C.B. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors thank Dr. Sara Hamilton for pilot reagents and helpful discussions, Dr. Marc Jenkins for the gift of soluble MHCII tetramers and biotinylated peptides for T cell analysis, Dr. Sunil David for performing the diphtheria antibody assay, and colleagues at the University of Minnesota Center for Immunology for advice.

Publisher Copyright:
© 2018 The Author(s).

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