Anti-cocaine vaccine based on coupling a cocaine analog to a disrupted adenovirus

George Koob, Martin J. Hicks, Sunmee Wee, Jonathan B. Rosenberg, Bishnu P. De, Stephen M. Kaminksy, Amira Moreno, Kim D. Janda, Ronald Crystal

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)899-904
Number of pages6
JournalCNS and Neurological Disorders - Drug Targets
Volume10
Issue number8
DOIs
Publication statusPublished - 1 Jan 2011
Externally publishedYes

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Keywords

  • Addiction
  • Adenovirus
  • Anti-cocaine antibody
  • Cocaine
  • Passive immunity
  • Vaccine

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pharmacology

Cite this

Koob, G., Hicks, M. J., Wee, S., Rosenberg, J. B., De, B. P., Kaminksy, S. M., Moreno, A., Janda, K. D., & Crystal, R. (2011). Anti-cocaine vaccine based on coupling a cocaine analog to a disrupted adenovirus. CNS and Neurological Disorders - Drug Targets, 10(8), 899-904. https://doi.org/10.2174/187152711799219334