Anti-Cocaine Vaccine Based on Coupling a Cocaine Analog to a Disrupted Adenovirus
Authors: Koob, George; J. Hicks, Martin; Wee, Sunmee; B. Rosenberg, Jonathan; P. De, Bishnu; M. Kaminksy, Stephen; Moreno, Amira; D. Janda, Kim; G. Crystal, Ronald
Source: CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders), Volume 10, Number 8, December 2011 , pp. 899-904(6)
Publisher: Bentham Science Publishers
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.
Keywords: Addiction; Adenovirus; Anti-coccaine antibody; Cocaine; E1-E3-; EDC; Laser evoked potential; Palmitoylethanolamide; Sensory nerve action potential; Vaccine; dAd5GNE; keyhole limpet hemocyanin; passive immunity
Document Type: Research Article
Publication date: December 1, 2011
- CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in neurological and CNS disorders. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.