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 Crystal

Research output: Contribution to journalArticle

22 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Dopamine Plasma Membrane Transport Proteins
Capsid
Cocaine
Adenoviridae
Primates
Vaccines
Cocaine-Related Disorders
Putamen
Capsid Proteins
Positron-Emission Tomography
Anti-Idiotypic Antibodies
Vaccination
Animal Models

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Adenovirus capsid-based anti-cocaine vaccine prevents cocaine from binding to the nonhuman primate CNS dopamine transporter. / Maoz, Anat; Hicks, Martin J.; Vallabhjosula, Shankar; Synan, Michael; Kothari, Paresh J.; Dyke, Jonathan P.; Ballon, Douglas J.; Kaminsky, Stephen M.; De, Bishnu P.; Rosenberg, Jonathan B.; Martinez, Diana; Koob, George F.; Janda, Kim D.; Crystal, Ronald.

In: Neuropsychopharmacology, Vol. 38, No. 11, 01.10.2013, p. 2170-2178.

Research output: Contribution to journalArticle

Maoz, A, Hicks, MJ, Vallabhjosula, S, Synan, M, Kothari, PJ, Dyke, JP, Ballon, DJ, Kaminsky, SM, De, BP, Rosenberg, JB, Martinez, D, Koob, GF, Janda, KD & Crystal, R 2013, 'Adenovirus capsid-based anti-cocaine vaccine prevents cocaine from binding to the nonhuman primate CNS dopamine transporter', Neuropsychopharmacology, vol. 38, no. 11, pp. 2170-2178. https://doi.org/10.1038/npp.2013.114
Maoz, Anat ; Hicks, Martin J. ; Vallabhjosula, Shankar ; Synan, Michael ; Kothari, Paresh J. ; Dyke, Jonathan P. ; Ballon, Douglas J. ; Kaminsky, Stephen M. ; De, Bishnu P. ; Rosenberg, Jonathan B. ; Martinez, Diana ; Koob, George F. ; Janda, Kim D. ; Crystal, Ronald. / Adenovirus capsid-based anti-cocaine vaccine prevents cocaine from binding to the nonhuman primate CNS dopamine transporter. In: Neuropsychopharmacology. 2013 ; Vol. 38, No. 11. pp. 2170-2178.
@article{154409d28a52467b877316a65ebc970f,
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 [ 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.",
keywords = "Addiction, Cocaine, Dopamine transporter (DAT), PET imaging, Vaccine",
author = "Anat Maoz and Hicks, {Martin J.} and Shankar Vallabhjosula and Michael Synan and Kothari, {Paresh J.} and Dyke, {Jonathan P.} and Ballon, {Douglas J.} and Kaminsky, {Stephen M.} and De, {Bishnu P.} and Rosenberg, {Jonathan B.} and Diana Martinez and Koob, {George F.} and Janda, {Kim D.} and Ronald Crystal",
year = "2013",
month = "10",
day = "1",
doi = "10.1038/npp.2013.114",
language = "English",
volume = "38",
pages = "2170--2178",
journal = "Neuropsychopharmacology",
issn = "0893-133X",
publisher = "Nature Publishing Group",
number = "11",

}

TY - JOUR

T1 - Adenovirus capsid-based anti-cocaine vaccine prevents cocaine from binding to the nonhuman primate CNS dopamine transporter

AU - Maoz, Anat

AU - Hicks, Martin J.

AU - Vallabhjosula, Shankar

AU - Synan, Michael

AU - Kothari, Paresh J.

AU - Dyke, Jonathan P.

AU - Ballon, Douglas J.

AU - Kaminsky, Stephen M.

AU - De, Bishnu P.

AU - Rosenberg, Jonathan B.

AU - Martinez, Diana

AU - Koob, George F.

AU - Janda, Kim D.

AU - Crystal, Ronald

PY - 2013/10/1

Y1 - 2013/10/1

N2 - 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.

AB - 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.

KW - Addiction

KW - Cocaine

KW - Dopamine transporter (DAT)

KW - PET imaging

KW - Vaccine

UR - http://www.scopus.com/inward/record.url?scp=84884283423&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84884283423&partnerID=8YFLogxK

U2 - 10.1038/npp.2013.114

DO - 10.1038/npp.2013.114

M3 - Article

C2 - 23660705

AN - SCOPUS:84884283423

VL - 38

SP - 2170

EP - 2178

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

SN - 0893-133X

IS - 11

ER -