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Neuropsychopharmacology. 2013 Oct;38(11):2170-8. doi: 10.1038/npp.2013.114. Epub 2013 May 10.

Adenovirus capsid-based anti-cocaine vaccine prevents cocaine from binding to the nonhuman primate CNS dopamine transporter.

Author information

1
1] Division of Nuclear Medicine and Molecular Imaging, Weill Cornell Medical College, New York, NY, USA [2] Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, NY, USA.

Abstract

Cocaine addiction is a major problem for which there is no approved pharmacotherapy. We have developed a vaccine to cocaine (dAd5GNE), based on the cocaine analog GNE linked to the capsid proteins of a serotype 5 adenovirus, designed to evoke anti-cocaine antibodies that sequester cocaine in the blood, preventing access to the CNS. To assess the efficacy of dAd5GNE in a large animal model, positron emission tomography (PET) and the radiotracer [(11)C]PE2I were used to measure cocaine occupancy of the dopamine transporter (DAT) in nonhuman primates. Repeat administration of dAd5GNE induced high anti-cocaine titers. Before vaccination, cocaine displaced PE2I from DAT in the caudate and putamen, resulting in 62±4% cocaine occupancy. In contrast, dAd5GNE-vaccinated animals showed reduced cocaine occupancy such that when anti-cocaine titers were >4 × 10(5), the cocaine occupancy was reduced to levels of <20%, significantly below the 47% threshold required to evoke the subjective 'high' reported in humans.

PMID:
23660705
PMCID:
PMC3773666
DOI:
10.1038/npp.2013.114
[Indexed for MEDLINE]
Free PMC Article

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