A synthetic opioid vaccine attenuates fentanyl-vs-food choice in male and female rhesus monkeys

• Published in: Drug and alcohol dependence Vol. 218; p. 108348
• Main Authors: Townsend, E. Andrew, Bremer, Paul T., Jacob, Nicholas T., Negus, S. Stevens, Janda, Kim D., Banks, Matthew L.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.01.2021; Elsevier Science Ltd
• Subjects: Affinity; Analgesics, Opioid - pharmacology; Animals; Antibodies; Attenuation; Buprenorphine; Candidates; Choice; Choice Behavior - drug effects; Clinical assessment; Concurrent schedule; Dose-Response Relationship, Drug; Drug addiction; Drug self-administration; Drugs; Feeding Behavior - drug effects; Female; Fentanyl; Fentanyl - pharmacology; Food; Immunization; Individual differences; Intravenous administration; Macaca mulatta; Male; Monkeys; Narcotics; Opioid vaccine; Opioid-Related Disorders; Opioids; Phylogeny; Primates; Rats; Reinforcement; Reinforcement, Psychology; Rhesus monkey; Robustness; Schedules; Self Administration; Substance use disorder; Vaccine efficacy; Vaccines; Fentanyl; Rhesus monkey; Drug self-administration; Choice; Opioid vaccine
• ISSN: 0376-8716; 1879-0046
• DOI: 10.1016/j.drugalcdep.2020.108348

•A fentanyl-targeted vaccine decreases choice of IV fentanyl over a food alternative in male and female rhesus monkeys.•Effectiveness of the fentanyl vaccine was similar to continuous buprenorphine treatment, but with a longer duration of action.•This vaccine formulation was stored at room temperature without any apparent degradation in its effectiveness. Opioid-targeted vaccines are under consideration as candidate Opioid Use Disorder medications. We recently reported that a fentanyl-targeted vaccine produced a robust and long-lasting attenuation of fentanyl-vs-food choice in rats. In the current study, we evaluated an optimized fentanyl-targeted vaccine in rhesus monkeys to determine whether vaccine effectiveness to attenuate fentanyl choice translated to a species with greater phylogenetic similarity to humans. Adult male (2) and female (3) rhesus monkeys were trained to respond under a concurrent schedule of food (1 g pellets) and intravenous fentanyl (0, 0.032−1 μg/kg/injection) reinforcement during daily 2 h sessions. Fentanyl choice dose-effect functions were determined daily and 7-day buprenorphine treatments (0.0032−0.032 mg/kg/h IV; n = 4–5) were determined for comparison to vaccine effects. Subsequently, a fentanyl-CRM197 conjugate vaccine was administered at week 0, 3, 8, 15 over a 29-week experimental period during which fentanyl choice dose-effect functions continued to be determined daily. Buprenorphine significantly decreased fentanyl choice and reciprocally increased food choice. Vaccination eliminated fentanyl choice and increased food choice in four-of-the-five monkeys. A transient and less robust vaccine effect was observed in the fifth monkey. Fentanyl-specific antibody concentrations peaked after the third vaccination to approximately 50 μg/mL while anti-fentanyl antibody affinity increased to a sustained low nanomolar level. These results translate fentanyl vaccine effectiveness from rats to rhesus monkeys to decrease fentanyl-vs-food choice, albeit with greater individual differences observed in monkeys. These results support the potential and further clinical evaluation of this fentanyl-targeted vaccine as a candidate Opioid Use Disorder medication.