title: Combatting Synthetic Designer Opioids: A Conjugate Vaccine Ablates Lethal Doses of Fentanyl Class Drugs.
abstract: 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.
authors.affiliation: Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, 10550 N Torrey Pines Rd BCC-582, La Jolla, CA, 92037, USA.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Bremer
authors.affiliation: Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, 10550 N Torrey Pines Rd BCC-582, La Jolla, CA, 92037, USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kimishima
authors.affiliation: Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, 10550 N Torrey Pines Rd BCC-582, La Jolla, CA, 92037, USA.
authors.forename: Joel E
authors.initials: JE
authors.lastname: Schlosburg
authors.affiliation: Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, 10550 N Torrey Pines Rd BCC-582, La Jolla, CA, 92037, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, 10550 N Torrey Pines Rd BCC-582, La Jolla, CA, 92037, USA.
authors.forename: Karen C
authors.initials: KC
authors.lastname: Collins
authors.affiliation: Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, 10550 N Torrey Pines Rd BCC-582, La Jolla, CA, 92037, USA. kdjanda@scripps.edu.
authors.forename: Kim D
authors.initials: KD
authors.lastname: Janda
mesh_terms: D000701:Analgesics, Opioid / Q000633:toxicity*; D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D015198:Designer Drugs / Q000138:chemical synthesis*; D005283:Fentanyl / Q000493:pharmacokinetics / Q000633:toxicity*; D051379:Mice; D014018:Tissue Distribution; D014612:Vaccines / Q000008:administration & dosage*
chemical_list: D000701:Analgesics, Opioid; D000931:Antidotes; D015198:Designer Drugs; D014612:Vaccines; D005283:Fentanyl
keywords: antibody; biosensors; conjugate vaccines; fentanyls; immunology