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

Townsend, E. Andrew ; Bremer, Paul T. ; Jacob, Nicholas T. ; Negus, S. Stevens ; Janda, Kim D. ; Banks, Matthew L.

Drug and alcohol dependence, 2021-01, Vol.218, p.108348-108348, Article 108348 [Periódico revisado por pares]

Ireland: Elsevier B.V

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Título:
A synthetic opioid vaccine attenuates fentanyl-vs-food choice in male and female rhesus monkeys
Autor: Townsend, E. Andrew ; Bremer, Paul T. ; Jacob, Nicholas T. ; Negus, S. Stevens ; Janda, Kim D. ; Banks, Matthew L.
Assuntos: 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
É parte de: Drug and alcohol dependence, 2021-01, Vol.218, p.108348-108348, Article 108348
Notas: Author contributions: EAT, MLB, and SSN conducted the behavioral experiments and analyzed the data. PTB, NTJ, KDJ conducted in-vitro experiments and analysis of blood samples. EAT and MLB designed the experiments and drafted the original manuscript. All authors critically reviewed the manuscript for content and approved the final manuscript version submitted for publication.
Descrição: •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.
Editor: Ireland: Elsevier B.V
Idioma: Inglês

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

Townsend, E. Andrew ; Bremer, Paul T. ; Jacob, Nicholas T. ; Negus, S. Stevens ; Janda, Kim D. ; Banks, Matthew L.

Ireland: Elsevier B.V

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