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 language | English |
---|---|
Pages (from-to) | 899-904 |
Number of pages | 6 |
Journal | CNS and Neurological Disorders - Drug Targets |
Volume | 10 |
Issue number | 8 |
DOIs | |
Publication status | Published - 1 Jan 2011 |
Externally published | Yes |
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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
}
TY - JOUR
T1 - Anti-cocaine vaccine based on coupling a cocaine analog to a disrupted adenovirus
AU - Koob, George
AU - Hicks, Martin J.
AU - Wee, Sunmee
AU - Rosenberg, Jonathan B.
AU - De, Bishnu P.
AU - Kaminksy, Stephen M.
AU - Moreno, Amira
AU - Janda, Kim D.
AU - Crystal, Ronald
PY - 2011/1/1
Y1 - 2011/1/1
N2 - 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.
AB - 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.
KW - Addiction
KW - Adenovirus
KW - Anti-cocaine antibody
KW - Cocaine
KW - Passive immunity
KW - Vaccine
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UR - http://www.scopus.com/inward/citedby.url?scp=84857751141&partnerID=8YFLogxK
U2 - 10.2174/187152711799219334
DO - 10.2174/187152711799219334
M3 - Article
C2 - 22229312
AN - SCOPUS:84857751141
VL - 10
SP - 899
EP - 904
JO - CNS and Neurological Disorders - Drug Targets
JF - CNS and Neurological Disorders - Drug Targets
SN - 1871-5273
IS - 8
ER -