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.