title: Efficacy of an adenovirus-based anti-cocaine vaccine to reduce cocaine self-administration and reacqusition using a choice procedure in rhesus macaques.
abstract: Immunopharmacotherapy offers an approach for treating cocaine abuse by specifically targeting the cocaine molecule and preventing its access to the CNS. dAd5GNE is a novel cocaine vaccine that attenuates the stimulant and the reinforcing effects of cocaine in rats. The goal of this study was to extend and validate dAd5GNE vaccine efficacy in non-human primates. Six experimentally naïve adult female rhesus monkeys (Macaca mulatta) were trained to self-administer 0.1mg/kg/injection intravenous (i.v.) cocaine or receive candy; then 4 monkeys were administered the vaccine and 2 monkeys were administered vehicle intramuscularly, with additional vaccine boosts throughout the study. The reinforcing effects of cocaine were measured during self-administration, extinction, and reacquisition (relapse) phases. Serum antibody titers in the vaccinated monkeys remained high throughout the study. There was no change in the preference for cocaine over candy over a 20-week period in 5 of the 6 monkeys; only one of the 4 (25%) vaccinated monkeys showed a decrease in cocaine choice. All 6 monkeys extinguished responding for cocaine during saline extinction testing; vaccinated monkeys tended to take longer to extinguish responding than control monkeys (17.5 vs. 7.0 sessions). Vaccination substantially retarded reacquisition of cocaine self-administration; control monkeys resumed cocaine self-administration within 6-41 sessions and 1 vaccinated monkey resumed cocaine self-administration in 19 sessions. The other 3 vaccinated monkeys required between 57 and 94 sessions to resume cocaine self-administration even in the context of employing several manipulations to encourage cocaine reacquisition. These data suggest that the dAdGNE vaccine may have therapeutic potential for humans who achieve cocaine abstinence as part of a relapse prevention strategy.
authors.affiliation: Department of Psychiatry, Division on Substance Abuse, New York State Psychiatric Institute, New York, NY, USA; Department of Psychiatry, Columbia University Medical Center, New York, NY, USA. Electronic address: se18@cumc.columbia.edu.
authors.forename: Suzette M
authors.initials: SM
authors.lastname: Evans
authors.affiliation: Department of Psychiatry, Division on Substance Abuse, New York State Psychiatric Institute, New York, NY, USA; Department of Psychiatry, Columbia University Medical Center, New York, NY, USA. Electronic address: rwf2@cumc.columbia.edu.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Foltin
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY, USA. Electronic address: mhicks@monmouth.edu.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Hicks
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY, USA. Electronic address: jor2024@med.cornell.edu.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Rosenberg
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY, USA. Electronic address: bpd2001@med.cornell.edu.
authors.forename: Bishnu P
authors.initials: BP
authors.lastname: De
authors.affiliation: Departments of Chemistry, Immunology and Microbial Science, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA. Electronic address: kdjanda@scripps.edu.
authors.forename: Kim D
authors.initials: KD
authors.lastname: Janda
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY, USA. Electronic address: smkamins@med.cornell.edu.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Kaminsky
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY, USA. Electronic address: geneticmedicine@med.cornell.edu.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000906:Antibodies / Q000097:blood; D002755:Choice Behavior / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage* / Q000276:immunology*; D005260:Female; D008253:Macaca mulatta; D008597:Menstrual Cycle / Q000187:drug effects; D012646:Self Administration; D014611:Vaccination; D014612:Vaccines / Q000627:therapeutic use*
chemical_list: D000906:Antibodies; D014612:Vaccines; D003042:Cocaine
keywords: Choice procedure; Cocaine; Relapse; Rhesus monkeys; Self-administration; Vaccine