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

Abstract

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.

• Authors: Sunmee Wee, Martin J Hicks, Bishnu P De, Jonathan B Rosenberg, Amira Y Moreno, Stephen M Kaminsky, Kim D Janda, Ronald G Crystal, George F Koob
• Journal: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (Neuropsychopharmacology) Vol. 37 Issue 5 Pg. 1083-91 (Apr 2012) ISSN: 1740-634X [Electronic] England
• PMID: 21918504 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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