Investigating the role of interleukin-4 in anti-opioid vaccine efficacy

Abstract

Abstract Vaccination against opioids is a novel therapeutic strategy to combat opioid use disorder (OUD) which can be used alone or in combination with currently available pharmacotherapies. Vaccination with opioid-carrier conjugates stimulates the production of opioid-specific antibodies that sequester the target drug in the serum and prevent distribution into the brain, attenuating the opioid’s pharmacological effects including analgesia, respiratory depression, and it’s reinforcing effects. An anti-oxycodone vaccine has shown promising preclinical efficacy, selectivity, and safety, and is now being tested in a Phase I clinical trial. Clinical trials for conjugate vaccines against cocaine and nicotine have shown that clinical efficacy is met in vaccinated subjects displaying high concentration of high affinity IgG titers. To increase anti-opioid vaccine clinical efficacy, we sought to elucidate their underlying immunobiology and identify predictive biomarkers of vaccine efficacy. Previously, our lab has found that the depletion of the cytokine interleukin-4 (IL-4) during anti-oxycodone immunization increases antibody titers, enhances class-switching from IgG1 to IgG2a, and leads to improved vaccine efficacy after oxycodone challenge in mice. Here, we investigated the association between increased IgG2a and improved vaccine efficacy by directly testing the role of this subclass during immune response after vaccination and during drug challenge. Furthermore, pre-immunization levels of IL-4 are explored as a predictive biomarker of vaccine efficacy in mice. Results from these studies will inform next generation vaccine design and biomarker identification in human clinical trial participants. Supported by grants from NIH (R01DA041730, T32DA007097, F31DA054760, HHSN272201800048C, U01DA051658)