Adenovirus capsid-based anti-cocaine vaccine prevents cocaine from binding to the nonhuman primate CNS dopamine transporter.
| Publication Type | Academic Article |
| Authors | Maoz A, Hicks M, Vallabhjosula S, Synan M, Kothari P, Dyke J, Ballon D, Kaminsky S, De B, Rosenberg J, Martinez D, Koob G, Janda K, Crystal R |
| Journal | Neuropsychopharmacology |
| Volume | 38 |
| Issue | 11 |
| Pagination | 2170-8 |
| Date Published | 05/10/2013 |
| ISSN | 1740-634X |
| Keywords | 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. |
| DOI | 10.1038/npp.2013.114 |
| PubMed ID | 23660705 |
| PubMed Central ID | PMC3773666 |