Cocaine Analog Coupled to Disrupted Adenovirus: A Vaccine Strategy to Evoke High-titer Immunity Against Addictive Drugs

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...

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Bibliographic Details
Published in:Molecular therapy 2011-03, Vol.19 (3), p.612-619
Main Authors: Hicks, Martin J, De, Bishnu P, Rosenberg, Jonathan B, Davidson, Jesse T, Moreno, Amira Y, Janda, Kim D, Wee, Sunmee, Koob, George F, Hackett, Neil R, Kaminsky, Stephen M, Worgall, Stefan, Toth, Miklos, Mezey, Jason G, Crystal, Ronald G
Format: Article
Language:English
Subjects:
Addictions
Adenoviridae - genetics
Adenovirus
Adenoviruses
Animals
Antibodies
Antibodies - blood
Cocaine
Cocaine - analogs & derivatives
Cocaine - immunology
Cocaine - metabolism
Defective Viruses - genetics
Defective Viruses - immunology
Defective Viruses - metabolism
Drugs
Female
Gene Transfer Techniques
Genetic Vectors - administration & dosage
Genetic Vectors - genetics
Locomotion - drug effects
Locomotion - immunology
Mice
Mice, Inbred BALB C
Motor Activity - drug effects
Motor Activity - immunology
Neurosciences
Original
Proteins
Substance-Related Disorders - immunology
Substance-Related Disorders - prevention & control
Vaccines
Vaccines - administration & dosage
Vaccines - immunology
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Summary: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.
ISSN:1525-0016
1525-0024
DOI:10.1038/mt.2010.280