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      G. Crystal

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: dAd5GNE, Cocaine, Addiction, Adenovirus, Vaccine, Anti-coccaine antibody, passive immunity, keyhole limpet hemocyanin, EDC, E1-E3-, Sensory nerve action potential, Palmitoylethanolamide, Laser evoked potential