Immuno-profiling of Individuals with Opioid Use Disorder : Insights for antibody development and immunological efficacy

Abstract

Abstract Opioid use disorders (OUD) and overdose are a public health emergency in the United States and worldwide. Immunotherapeutics such as vaccines and monoclonal antibodies (mAbs) offer potential solutions in treatment and prevention of OUD and overdose. To accelerate their translation, our work focuses on immunoprofiling of opioid-specific antibodies and B cell repertoires in drug-naive individuals and those with OUD. Using antigen-based enrichment paired with flow cytometry, we found that individuals with OUD display increased frequency of opioid-specific B cells. When the individuals with OUD are compared to the drug-naive individuals, the increased opioid-induced B cell population was not paired with increased opioid-specific IgG polyclonal antibodies, changes in the B cell repertoires were associated with cytokine patterns. Sequencing of the B cell receptor (BCR) revealed that opioids affect the V(D)J rearrangement in B cells, as shown by isolation of a human mid-affinity monoclonal antibody against oxycodone and morphine. Results indicate that immunoprofiling could corroborate diagnosis of OUD, and could provide biomarkers to support testing of novel immunotherapeutics in individuals with OUD. Supported by grants from NIH U01 DA051658 Antibody-based countermeasures against fentanyl and its analogs and UG3 DA 0477117 Phase 1a/1b clinical trials of multivalent opioid vaccine components.