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

Anat Maoz, Martin J. Hicks, Shankar Vallabhjosula, Michael Synan, Paresh J. Kothari, Jonathan P. Dyke, Douglas J. Ballon, Stephen M. Kaminsky, Bishnu P. De, Jonathan B. Rosenberg, Diana Martinez, George F. Koob, Kim D. Janda, Ronald G. Crystal

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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 [ 11C]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, dAd5GNEvaccinated animals showed reduced cocaine occupancy such that when anti-cocaine titers were >4×105, the cocaine occupancy was reduced to levels of <20%, significantly below the 47% threshold required to evoke the subjective 'high' reported in humans.

Original languageEnglish
Pages (from-to)2170-2178
Number of pages9
JournalNeuropsychopharmacology
Volume38
Issue number11
DOIs
Publication statusPublished - 1 Oct 2013

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Keywords

  • Addiction
  • Cocaine
  • Dopamine transporter (DAT)
  • PET imaging
  • Vaccine

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Maoz, A., Hicks, M. J., Vallabhjosula, S., Synan, M., Kothari, P. J., Dyke, J. P., Ballon, D. J., Kaminsky, S. M., De, B. P., Rosenberg, J. B., Martinez, D., Koob, G. F., Janda, K. D., & Crystal, R. G. (2013). Adenovirus capsid-based anti-cocaine vaccine prevents cocaine from binding to the nonhuman primate CNS dopamine transporter. Neuropsychopharmacology, 38(11), 2170-2178. https://doi.org/10.1038/npp.2013.114