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

13 de janeiro de 20116min

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 Mezey1,5 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 E1E3 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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A Unidade de Pesquisa em álcool e Drogas (UNIAD) foi fundada em 1994 pelo Prof. Dr. Ronaldo Laranjeira e John Dunn, recém-chegados da Inglaterra. A criação contou, na época, com o apoio do Departamento de Psiquiatria da UNIFESP. Inicialmente (1994-1996) funcionou dentro do Complexo Hospital São Paulo, com o objetivo de atender funcionários dependentes.



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