AAVrh.10-mediated expression of an anti-cocaine antibody mediates persistent passive immunization that suppresses cocaine-induced behavior.

Publication Type	Academic Article
Authors	Rosenberg J, Hicks M, De B, Pagovich O, Frenk E, Janda K, Wee S, Koob G, Hackett N, Kaminsky S, Worgall S, Tignor N, Mezey J, Crystal R
Journal	Hum Gene Ther
Volume	23
Issue	5
Pagination	451-9
Date Published	05/01/2012
ISSN	1557-7422
Keywords	Antibodies, Monoclonal, Cocaine, Cocaine-Related Disorders, Genetic Therapy, Immunization, Passive
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.
DOI	10.1089/hum.2011.178
PubMed ID	22486244
PubMed Central ID	PMC3360503