Anti-cocaine vaccine based on coupling a cocaine analog to a disrupted adenovirus.
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.
Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
George
G
Koob
Martin J
MJ
Hicks
Sunmee
S
Wee
Jonathan B
JB
Rosenberg
Bishnu P
BP
De
Stephen M
SM
Kaminsky
Amira
A
Moreno
Kim D
KD
Janda
Ronald G
RG
Crystal
D000256:Adenoviridae / Q000276:immunology; D000818:Animals; D003042:Cocaine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000276:immunology*; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007116:Immunization, Passive / Q000379:methods; D014612:Vaccines / Q000276:immunology / Q000627:therapeutic use*
D014612:Vaccines; D003042:Cocaine