Combatting Synthetic Designer Opioids: A Conjugate Vaccine Ablates Lethal Doses of Fentanyl Class Drugs

• Published in: Angewandte Chemie International Edition Vol. 55; no. 11; pp. 3772 - 3775
• Main Authors: Bremer, Paul T., Kimishima, Atsushi, Schlosburg, Joel E., Zhou, Bin, Collins, Karen C., Janda, Kim D.
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 07.03.2016; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Ablation; Abuse; Analgesics, Opioid - toxicity; Analytical methods; Animals; Antibodies; antibody; Antidotes - therapeutic use; biosensors; conjugate vaccines; Cross-reactivity; Designer Drugs - chemical synthesis; Drug abuse; Drug addiction; Drug dosages; Drugs; Fentanyl; Fentanyl - pharmacokinetics; Fentanyl - toxicity; fentanyls; immunology; Immunotherapy; Mice; Morphine; Narcotics; Opioids; Overdose; Pain management; Surface plasmon resonance; Tissue Distribution; Toxicology; Vaccines; Vaccines - administration & dosage; biosensors; antibody; fentanyls; immunology; conjugate vaccines
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201511654

Fentanyl is an addictive prescription opioid that is over 80 times more potent than morphine. The synthetic nature of fentanyl has enabled the creation of dangerous “designer drug” analogues that escape toxicology screening, yet display comparable potency to the parent drug. Alarmingly, a large number of fatalities have been linked to overdose of fentanyl derivatives. Herein, we report an effective immunotherapy for reducing the psychoactive effects of fentanyl class drugs. A single conjugate vaccine was created that elicited high levels of antibodies with cross‐reactivity for a wide panel of fentanyl analogues. Moreover, vaccinated mice gained significant protection from lethal fentanyl doses. Lastly, a surface plasmon resonance (SPR)‐based technique was established enabling drug‐specificity profiling of antibodies derived directly from serum. Our newly developed fentanyl vaccine and analytical methods may assist in the battle against synthetic opioid abuse. Addiction therapy: Fentanyls are potent and addictive opioids implicated in many overdose deaths. A conjugate vaccine against fentanyl and fentanyl analogues was developed, which protected mice from lethal drug doses. A robust SPR‐based biosensor was created to profile the low‐nanomolar affinities of serum antibodies for various fentanyl analogues.