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 journal › Article

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

Fingerprint

Cocaine
Adenoviridae
Vaccines
Capsid Proteins
Self Administration
Haptens
Toxicology
Anti-Idiotypic Antibodies
Immune System
Immunoglobulin G
Antibodies
Brain

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pharmacology

Cite this

Anti-cocaine vaccine based on coupling a cocaine analog to a disrupted adenovirus. / Koob, George; Hicks, Martin J.; Wee, Sunmee; Rosenberg, Jonathan B.; De, Bishnu P.; Kaminksy, Stephen M.; Moreno, Amira; Janda, Kim D.; Crystal, Ronald.

In: CNS and Neurological Disorders - Drug Targets, Vol. 10, No. 8, 01.01.2011, p. 899-904.

Research output: Contribution to journal › Article

Koob, G, Hicks, MJ, Wee, S, Rosenberg, JB, De, BP, Kaminksy, SM, Moreno, A, Janda, KD & Crystal, R 2011, 'Anti-cocaine vaccine based on coupling a cocaine analog to a disrupted adenovirus', CNS and Neurological Disorders - Drug Targets, vol. 10, no. 8, pp. 899-904. https://doi.org/10.2174/187152711799219334
Koob G, Hicks MJ, Wee S, Rosenberg JB, De BP, Kaminksy SM et al. Anti-cocaine vaccine based on coupling a cocaine analog to a disrupted adenovirus. CNS and Neurological Disorders - Drug Targets. 2011 Jan 1;10(8):899-904. https://doi.org/10.2174/187152711799219334
Koob, George ; Hicks, Martin J. ; Wee, Sunmee ; Rosenberg, Jonathan B. ; De, Bishnu P. ; Kaminksy, Stephen M. ; Moreno, Amira ; Janda, Kim D. ; Crystal, Ronald. / Anti-cocaine vaccine based on coupling a cocaine analog to a disrupted adenovirus. In: CNS and Neurological Disorders - Drug Targets. 2011 ; Vol. 10, No. 8. pp. 899-904.
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