Anti-cocaine vaccine based on coupling a cocaine analog to a disrupted adenovirus.
Publication Type | Review |
Authors | Koob G, Hicks M, Wee S, Rosenberg J, De B, Kaminsky S, Moreno A, Janda K, Crystal R |
Journal | CNS Neurol Disord Drug Targets |
Volume | 10 |
Issue | 8 |
Pagination | 899-904 |
Date Published | 12/01/2011 |
ISSN | 1996-3181 |
Keywords | Adenoviridae, Cocaine, Cocaine-Related Disorders, Vaccines |
Abstract | The challenge in developing an anti-cocaine vaccine is that cocaine is a small molecule, invisible to the immune system. Leveraging the knowledge that adenovirus (Ad) capsid proteins are highly immunogenic in humans, we hypothesized that linking a cocaine hapten to Ad capsid proteins would elicit high-affinity, high-titer antibodies against cocaine, sufficient to sequester systemically administered cocaine and prevent access to the brain, thus suppressing cocaine-induced behaviors. Based on these concepts, we developed dAd5GNE, a disrupted E1-E3- serotype 5 Ad with GNE, a stable cocaine analog, covalently linked to the Ad capsid proteins. In pre-clinical studies, dAd5GNE evoked persistent, high titer, high affinity IgG anti-cocaine antibodies, and was highly effective in blocking cocaine-induced hyperactivity and cocaine self-administration behavior in rats. Future studies will be designed to expand the efficacy studies, carry out relevant toxicology studies, and test dAd5GNE in human cocaine addicts. |
DOI | 10.2174/187152711799219334 |
PubMed ID | 22229312 |
PubMed Central ID | PMC3369545 |