Efficacy of an adenovirus-based anti-cocaine vaccine to reduce cocaine self-administration and reacquisition using a choice procedure in rhesus macaques.

Publication TypeJournal Article
Year of Publication2016
AuthorsEvans SM, Foltin RW, Hicks MJ, Rosenberg JB, De BP, Janda KD, Kaminsky SM, Crystal RG
JournalPharmacol Biochem Behav
Date Published2016 Nov - Dec
KeywordsAdenoviridae, Animals, Antibodies, Choice Behavior, Cocaine, Female, Macaca mulatta, Menstrual Cycle, Self Administration, Vaccination, Vaccines

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.

Alternate JournalPharmacol. Biochem. Behav.
PubMed ID27697554
PubMed Central IDPMC5145743
Grant ListK05 DA031749 / DA / NIDA NIH HHS / United States
RC2 DA028847 / DA / NIDA NIH HHS / United States
T32 HL094284 / HL / NHLBI NIH HHS / United States