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

Jonathan B. Rosenberg, Martin J. Hicks, Bishnu P. De, Odelya Pagovich, Esther Frenk, Kim D. Janda, Sunmee Wee, George F. Koob, Neil R. Hackett, Stephen M. Kaminsky, Stefan Worgall, Nicole Tignor, Jason G. Mezey, Ronald G. Crystal

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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.

Original languageEnglish
Pages (from-to)451-459
Number of pages9
JournalHuman gene therapy
Volume23
Issue number5
DOIs
Publication statusPublished - 1 May 2012

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Rosenberg, J. B., Hicks, M. J., De, B. P., Pagovich, O., Frenk, E., Janda, K. D., Wee, S., Koob, G. F., Hackett, N. R., Kaminsky, S. M., Worgall, S., Tignor, N., Mezey, J. G., & Crystal, R. G. (2012). AAVrh.10-mediated expression of an anti-cocaine antibody mediates persistent passive immunization that suppresses cocaine-induced behavior. Human gene therapy, 23(5), 451-459. https://doi.org/10.1089/hum.2011.178