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

Overview

MeSH

  • Adenoviridae
  • Animals
  • Capsid
  • Carbon Radioisotopes
  • Caudate Nucleus
  • Female
  • Macaca mulatta
  • Neuroimaging
  • Nortropanes
  • Putamen
  • Radioligand Assay
  • Radionuclide Imaging

MeSH Major

  • Antibodies
  • Cocaine
  • Dopamine Plasma Membrane Transport Proteins
  • Vaccines

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.

publication date

  • October 2013

has subject area

  • Adenoviridae
  • Animals
  • Antibodies
  • Capsid
  • Carbon Radioisotopes
  • Caudate Nucleus
  • Cocaine
  • Dopamine Plasma Membrane Transport Proteins
  • Female
  • Macaca mulatta
  • Neuroimaging
  • Nortropanes
  • Putamen
  • Radioligand Assay
  • Radionuclide Imaging
  • Vaccines

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3773666

Digital Object Identifier (DOI)

  • 10.1038/npp.2013.114

PubMed ID

  • 23660705

Additional Document Info

start page

  • 2170

end page

  • 2178

volume

  • 38

number

  • 11