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

Original Article

Subject Category: Vaccine Technology

Molecular Therapy (2010); doi:10.1038/mt.2010.280

Martin J Hicks¹, Bishnu P De¹, Jonathan B Rosenberg¹, Jesse T Davidson¹, Amira Y Moreno², Kim D Janda², Sunmee Wee³, George F Koob³, Neil R Hackett¹, Stephen M Kaminsky¹, Stefan Worgall¹, Miklos Toth⁴, Jason G Mezey^1,5 and Ronald G Crystal¹

1. ¹Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA
2. ²Department of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, La Jolla, California, USA
3. ³Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California, USA
4. ⁴Department of Pharmacology, Weill Cornell Medical College, New York, New York, USA
5. ⁵Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, USA

Correspondence: Ronald G Crystal, Department of Genetic Medicine, Weill Cornell Medical College, 1300 York Avenue, Box 96, New York, New York 10065, USA. E-mail: geneticmedicine@med.cornell.edu

The first three authors contributed equally to this work.

Received 24 August 2010; Accepted 21 November 2010; Published online 4 January 2011.

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.