title: Adenovirus capsid-based anti-cocaine vaccine prevents cocaine from binding to the nonhuman primate CNS dopamine transporter.
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.
authors: 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.
authors: Anat
authors: A
authors: Maoz
authors: Martin J
authors: MJ
authors: Hicks
authors: Shankar
authors: S
authors: Vallabhjosula
authors: Michael
authors: M
authors: Synan
authors: Paresh J
authors: PJ
authors: Kothari
authors: Jonathan P
authors: JP
authors: Dyke
authors: Douglas J
authors: DJ
authors: Ballon
authors: Stephen M
authors: SM
authors: Kaminsky
authors: Bishnu P
authors: BP
authors: De
authors: Jonathan B
authors: JB
authors: Rosenberg
authors: Diana
authors: D
authors: Martinez
authors: George F
authors: GF
authors: Koob
authors: Kim D
authors: KD
authors: Janda
authors: Ronald G
authors: RG
authors: Crystal
mesh_terms: D000256:Adenoviridae / Q000737:chemistry; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D002213:Capsid / Q000378:metabolism; D002250:Carbon Radioisotopes; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D008253:Macaca mulatta; D059906:Neuroimaging; D009662:Nortropanes / Q000138:chemical synthesis; D011699:Putamen / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay; D011877:Radionuclide Imaging; D014612:Vaccines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C582059:6-(3-(benzoyloxy)-8-methyl-8-azabicyclo(3.2.1)octane-2-carboxoamido)hexanoic acid; D000906:Antibodies; D002250:Carbon Radioisotopes; D050483:Dopamine Plasma Membrane Transport Proteins; C113010:N-(3-iodoprop-2-enyl)-2-beta-carbomethoxy-3-(4-methylphenyl)nortropane; D009662:Nortropanes; D014612:Vaccines; D003042:Cocaine
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