Novel cocaine vaccine linked to a disrupted adenovirus gene transfer vector blocks cocaine psychostimulant and reinforcing effects

Neuropsychopharmacology. 2012 Apr;37(5):1083-91. doi: 10.1038/npp.2011.200. Epub 2011 Sep 14.


Immunotherapy is a promising treatment for drug addiction. However, insufficient immune responses to vaccines in most subjects pose a challenge. In this study, we tested the efficacy of a new cocaine vaccine (dAd5GNE) in antagonizing cocaine addiction-related behaviors in rats. This vaccine used a disrupted serotype 5 adenovirus (Ad) gene transfer vector coupled to a third-generation cocaine hapten, termed GNE (6-(2R,3S)-3-(benzoyloxy)-8-methyl-8-azabicyclo [3.2.1] octane-2-carboxamido-hexanoic acid). Three groups of rats were immunized with dAd5GNE. One group was injected with (3)H-cocaine, and radioactivity in the blood and brain was determined. A second group was tested for cocaine-induced locomotor sensitization. A third group was examined for cocaine self-administration, extinction, and reinstatement of responding for cocaine. Antibody titers were determined at various time-points. In each experiment, we added a control group that was immunized with dAd5 without a hapten. The vaccination with dAd5GNE produced long-lasting high titers (>10(5)) of anti-cocaine antibodies in all of the rats. The vaccination inhibited cocaine-induced hyperlocomotor activity and sensitization. Vaccinated rats acquired cocaine self-administration, but they showed less motivation to self-administer cocaine under a progressive-ratio schedule than control rats. When cocaine was not available in a session, control rats exhibited 'extinction burst' responding, whereas vaccinated rats did not. Moreover, when primed with cocaine, vaccinated rats did not reinstate responding, suggesting a blockade of cocaine-seeking behavior. These data strongly suggest that our dAd5GNE vector-based vaccine may be effective in treating cocaine abuse and addiction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Analysis of Variance
  • Animals
  • Brain / metabolism
  • Central Nervous System Stimulants
  • Cocaine / administration & dosage
  • Cocaine / immunology*
  • Cocaine / pharmacokinetics
  • Cocaine-Related Disorders / prevention & control*
  • Cocaine-Related Disorders / psychology
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology
  • Disease Models, Animal
  • Dopamine Uptake Inhibitors / administration & dosage
  • Dopamine Uptake Inhibitors / immunology*
  • Dopamine Uptake Inhibitors / pharmacokinetics
  • Extinction, Psychological / drug effects
  • Genetic Vectors / administration & dosage
  • Haptens
  • Immunoglobulin G / blood
  • Male
  • Methamphetamine / pharmacology
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Radioimmunoassay / methods
  • Rats
  • Rats, Wistar
  • Reinforcement, Psychology*
  • Self Administration
  • Time Factors
  • Transfer, Psychology / drug effects
  • Tritium / pharmacokinetics
  • Vaccination / methods*


  • Central Nervous System Stimulants
  • Dopamine Uptake Inhibitors
  • Haptens
  • Immunoglobulin G
  • Tritium
  • Methamphetamine
  • Cocaine