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

被引:113
作者
Bremer, Paul T. [1 ,2 ]
Kimishima, Atsushi [1 ,2 ]
Schlosburg, Joel E. [1 ,2 ]
Zhou, Bin [1 ,2 ]
Collins, Karen C. [1 ,2 ]
Janda, Kim D. [1 ,2 ]
机构
[1] Scripps Res Inst, WIRM, Skaggs Inst Chem Biol, Dept Chem, 10550 N Torrey Pines Rd BCC 582, La Jolla, CA 92037 USA
[2] Scripps Res Inst, WIRM, Skaggs Inst Chem Biol, Dept Immunol, 10550 N Torrey Pines Rd BCC 582, La Jolla, CA 92037 USA
关键词
antibody; biosensors; conjugate vaccines; fentanyls; immunology; HAPTEN; HEROIN; GLYCOPEPTIDES; AGONIST; BINDING; RELAPSE; IMPACT; TN;
D O I
10.1002/anie.201511654
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
收藏
页码:3772 / 3775
页数:4
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