Vaccine blunts fentanyl potency in male rhesus monkeys

Abstract

AbstractOne proposed factor contributing to the increased opioid overdose deaths is the increased frequency of synthetic opioids, including fentanyl and fentanyl analogs. A treatment strategy currently under development to address the ongoing opioid crisis is immunopharmacotherapies or opioid-targeted vaccines. The present study determined the effectiveness and selectivity of a fentanyl-tetanus toxoid conjugate vaccine to alter the behavioral effects of fentanyl and a structurally dissimilar mu-opioid agonist oxycodone in male rhesus monkeys (n=3-4). Fentanyl and oxycodone produced dose-dependent suppression of behavior in an assay of schedule-controlled responding and antinociception in an assay of thermal nociception (50°C). Acute naltrexone (0.032 mg/kg) produced an approximate 10-fold potency shift for fentanyl to decrease operant responding. The fentanyl vaccine was administered at weeks 0, 2, 4, 9, 19, and 44 and fentanyl or oxycodone potencies in both behavioral assays were redetermined over the course of 49 weeks. The vaccine significantly and selectively shifted fentanyl potency at least 10-fold in both assays at several time points over the entire experimental period. Mid-point titer levels were significantly correlated with fentanyl antinociceptive potency shifts. Antibody affinity for fentanyl as measured by a competitive binding assay increased over time to around 3-4 nM. The fentanyl vaccine also significantly increased fentanyl plasma levels approximately 6-fold consistent with the hypothesis that the vaccine sequesters fentanyl in the blood. Overall, these results support the continued development and evaluation of this fentanyl vaccine to address the ongoing opioid crisis.HighlightsVaccine blunted fentanyl rate-suppression potency ∼ 10-foldVaccine blunted fentanyl antinociceptive potency ∼25-foldFentanyl vaccine was as effective as acute 0.032 mg/kg naltrexoneVaccine was selective for fentanyl and not oxycodoneAntibody immune response ∼ 3 nM affinity for fentanyl