title: AAVrh.10-mediated expression of an anti-cocaine antibody mediates persistent passive immunization that suppresses cocaine-induced behavior.
abstract: Cocaine addiction is a major problem affecting all societal and economic classes for which there is no effective therapy. We hypothesized an effective anti-cocaine vaccine could be developed by using an adeno-associated virus (AAV) gene transfer vector as the delivery vehicle to persistently express an anti-cocaine monoclonal antibody in vivo, which would sequester cocaine in the blood, preventing access to cognate receptors in the brain. To accomplish this, we constructed AAVrh.10antiCoc.Mab, an AAVrh.10 gene transfer vector expressing the heavy and light chains of the high affinity anti-cocaine monoclonal antibody GNC92H2. Intravenous administration of AAVrh.10antiCoc.Mab to mice mediated high, persistent serum levels of high-affinity, cocaine-specific antibodies that sequestered intravenously administered cocaine in the blood. With repeated intravenous cocaine challenge, naive mice exhibited hyperactivity, while the AAVrh.10antiCoc.Mab-vaccinated mice were completely resistant to the cocaine. These observations demonstrate a novel strategy for cocaine addiction by requiring only a single administration of an AAV vector mediating persistent, systemic anti-cocaine passive immunity.
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Rosenberg
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Hicks
authors.forename: Bishnu P
authors.initials: BP
authors.lastname: De
authors.forename: Odelya
authors.initials: O
authors.lastname: Pagovich
authors.forename: Esther
authors.initials: E
authors.lastname: Frenk
authors.forename: Kim D
authors.initials: KD
authors.lastname: Janda
authors.forename: Sunmee
authors.initials: S
authors.lastname: Wee
authors.forename: George F
authors.initials: GF
authors.lastname: Koob
authors.forename: Neil R
authors.initials: NR
authors.lastname: Hackett
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Kaminsky
authors.forename: Stefan
authors.initials: S
authors.lastname: Worgall
authors.forename: Nicole
authors.initials: N
authors.lastname: Tignor
authors.forename: Jason G
authors.initials: JG
authors.lastname: Mezey
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000097:blood / Q000235:genetics*; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000493:pharmacokinetics; D019970:Cocaine-Related Disorders / Q000628:therapy*; D000229:Dependovirus; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D057809:HEK293 Cells; D000882:Haplorhini; D006801:Humans; D007116:Immunization, Passive / Q000379:methods*; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D014612:Vaccines; D003042:Cocaine