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

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2016年 / 55卷 / 11期

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

页码：3772 / 3775

页数：4

共 35 条

[1]

Bannon Anthony W, 2007, Curr Protoc Neurosci, VChapter 8, DOI 10.1002/0471142301.ns0809s41

[2] Injection Route and TLR9 Agonist Addition Significantly Impact Heroin Vaccine Efficacy [J].

Bremer, Paul T. ;

Schlosburg, Joel E. ;

Lively, Jenny M. ;

Janda, Kim D. .

MOLECULAR PHARMACEUTICS, 2014, 11 (03) :1075-1080

[3] Investigating the Effects of a Hydrolytically Stable Hapten and a Th1 Adjuvant on Heroin Vaccine Performance [J].

Bremer, Paul T. ;

Janda, Kim D. .

JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (23) :10776-10780

[4] Cocaine vaccines: Antibody protection against relapse in a rat model [J].

Carrera, MRA ;

Ashley, JA ;

Zhou, B ;

Wirsching, P ;

Koob, GF ;

Janda, KD .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (11) :6202-6206

[5] Designer drugs: a medicinal chemistry perspective [J].

Carroll, F. Ivy ;

Lewin, Anita H. ;

Mascarella, S. Wayne ;

Seltzman, Herbert H. ;

Reddy, P. Anantha .

ADDICTION REVIEWS, 2012, 1248 :18-38

[6] Investigating Hapten Clustering as a Strategy to Enhance Vaccines against Drugs of Abuse [J].

Collins, Karen C. ;

Janda, Kim D. .

BIOCONJUGATE CHEMISTRY, 2014, 25 (03) :593-600

[7] Bath salts and synthetic cathinones: An emerging designer drug phenomenon [J].

German, Christopher L. ;

Fleckenstein, Annette E. ;

Hanson, Glen R. .

LIFE SCIENCES, 2014, 97 (01) :2-8

[8]

HENDERSON GL, 1988, J FORENSIC SCI, V33, P569

[9]

HENDERSON GL, 1991, J FORENSIC SCI, V36, P422

[10] Efficacy, but Not Antibody Titer or Affinity, of a Heroin Hapten Conjugate Vaccine Correlates with Increasing Hapten Densities on Tetanus Toxoid, but Not on CRM197 Carriers [J].

Jalah, Rashmi ;

Torres, Oscar B. ;

Mayorov, Alexander V. ;

Li, Fuying ;

Antoline, Joshua F. G. ;

Jacobson, Arthur E. ;

Rice, Kenner C. ;

Deschamps, Jeffrey R. ;

Beck, Zoltan ;

Alving, Carl R. ;

Matyas, Gary R. .

BIOCONJUGATE CHEMISTRY, 2015, 26 (06) :1041-1053

← 1 2 3 4 →