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

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 numb...

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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
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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. 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.
AbstractList	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. 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. Fentanyl is an addictive prescription opioid that is over 80times 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.
Author	Zhou, Bin Janda, Kim D. Bremer, Paul T. Collins, Karen C. Kimishima, Atsushi Schlosburg, Joel E.
Author_xml	– sequence: 1 givenname: Paul T. surname: Bremer fullname: Bremer, Paul T. organization: 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, CA, 92037, La Jolla, USA – sequence: 2 givenname: Atsushi surname: Kimishima fullname: Kimishima, Atsushi organization: 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, CA, 92037, La Jolla, USA – sequence: 3 givenname: Joel E. surname: Schlosburg fullname: Schlosburg, Joel E. organization: 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, CA, 92037, La Jolla, USA – sequence: 4 givenname: Bin surname: Zhou fullname: Zhou, Bin organization: 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, CA, 92037, La Jolla, USA – sequence: 5 givenname: Karen C. surname: Collins fullname: Collins, Karen C. organization: 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, CA, 92037, La Jolla, USA – sequence: 6 givenname: Kim D. surname: Janda fullname: Janda, Kim D. email: kdjanda@scripps.edu organization: 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, CA, 92037, La Jolla, USA
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Copyright	2016 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Snippet	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... Fentanyl is an addictive prescription opioid that is over 80times more potent than morphine. The synthetic nature of fentanyl has enabled the creation of...
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SubjectTerms	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
Title	Combatting Synthetic Designer Opioids: A Conjugate Vaccine Ablates Lethal Doses of Fentanyl Class Drugs
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