title: Fate of systemically administered cocaine in nonhuman primates treated with the dAd5GNE anticocaine vaccine.
abstract: Cocaine use disorders are mediated by the cocaine blockade of the dopamine transporter in the central nervous system (CNS). On the basis of the concept that these effects could be obviated if cocaine were prevented from reaching its cognate receptors in the CNS, we have developed an anticocaine vaccine, dAd5GNE, based on a cocaine analog covalently linked to capsid proteins of an E1(-)E3(-) serotype 5 adenovirus. While the vaccine effectively blocks systemically administered cocaine from reaching the brain by mediating sequestration of the cocaine in the blood, the fact that cocaine also has significant peripheral effects raises concerns that vaccination-mediated redistribution could lead to adverse effects in the visceral organs. The distribution of systemically administered cocaine at a weight-adjusted typical human dose was evaluated along with cocaine metabolites in both dAd5GNE-vaccinated and control nonhuman primates. dAd5GNE sequestration of cocaine to the blood not only prevented cocaine access to the CNS, but also limited access of both the drug and its metabolites to other cocaine-sensitive organs. The levels of cocaine in the blood of vaccinated animals rapidly decreased, suggesting that while the antibody limits access of the drug and its active metabolites to the brain and sensitive organs of the periphery, it does not prolong drug levels in the blood compartment. Gross and histopathology of major organs found no vaccine-mediated untoward effects. These results build on our earlier measures of efficacy and demonstrate that the dAd5GNE vaccine-mediated redistribution of administered cocaine is not likely to impact the vaccine safety profile.
authors.affiliation: 1 Department of Genetic Medicine, Weill Cornell Medical College , New York, NY 10065.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Hicks
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Kaminsky
authors.forename: Bishnu P
authors.initials: BP
authors.lastname: De
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Rosenberg
authors.forename: Suzette M
authors.initials: SM
authors.lastname: Evans
authors.forename: Richard W
authors.initials: RW
authors.lastname: Foltin
authors.forename: David M
authors.initials: DM
authors.lastname: Andrenyak
authors.forename: David E
authors.initials: DE
authors.lastname: Moody
authors.forename: George F
authors.initials: GF
authors.lastname: Koob
authors.forename: Kim D
authors.initials: KD
authors.lastname: Janda
authors.forename: Rodolfo J
authors.initials: RJ
authors.lastname: Ricart Arbona
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Lepherd
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects; D003042:Cocaine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000628:therapy*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D005260:Female; D016233:Immunotherapy, Active; D008253:Macaca mulatta; D014611:Vaccination; D014612:Vaccines
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D014612:Vaccines; C008671:norcocaine; C005618:benzoylecgonine; D003042:Cocaine; C034524:ecgonine methyl ester