Adenovirus Capsid-Based Anti-Cocaine Vaccine Prevents Cocaine from Binding to the Nonhuman Primate CNS Dopamine Transporter

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 [C-11]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 x 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.