Cocaine analog coupled to disrupted adenovirus: a vaccine strategy to evoke high-titer immunity against addictive drugs

可卡因类似物与破坏的腺病毒偶联:一种激发对成瘾药物高滴度免疫力的疫苗策略

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作者:Martin J Hicks, Bishnu P De, Jonathan B Rosenberg, Jesse T Davidson, Amira Y Moreno, Kim D Janda, Sunmee Wee, George F Koob, Neil R Hackett, Stephen M Kaminsky, Stefan Worgall, Miklos Toth, Jason G Mezey, Ronald G Crystal

Abstract

Based on the concept that anticocaine antibodies could prevent inhaled cocaine from reaching its target receptors in the brain, an effective anticocaine vaccine could help reverse cocaine addiction. Leveraging the knowledge that E1(-)E3(-) adenovirus (Ad) gene transfer vectors are potent immunogens, we have developed a novel vaccine platform for addictive drugs by covalently linking a cocaine analog to the capsid proteins of noninfectious, disrupted Ad vector. The Ad-based anticocaine vaccine evokes high-titer anticocaine antibodies in mice sufficient to completely reverse, on a persistent basis, the hyperlocomotor activity induced by intravenous administration of cocaine.

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