AAV-directed persistent expression of a gene encoding anti-nicotine antibody for smoking cessation.

Publication Type	Academic Article
Authors	Hicks M, Rosenberg J, De B, Pagovich O, Young C, Qiu J, Kaminsky S, Hackett N, Worgall S, Janda K, Davisson R, Crystal R
Journal	Sci Transl Med
Volume	4
Issue	140
Pagination	140ra87
Date Published	06/27/2012
ISSN	1946-6242
Keywords	Antibodies, Monoclonal, Dependovirus, Nicotine, Smoking Cessation
Abstract	Current strategies to help tobacco smokers quit have limited success as a result of the addictive properties of the nicotine in cigarette smoke. We hypothesized that a single administration of an adeno-associated virus (AAV) gene transfer vector expressing high levels of an anti-nicotine antibody would persistently prevent nicotine from reaching its receptors in the brain. To test this hypothesis, we constructed an AAVrh.10 vector that expressed a full-length, high-affinity, anti-nicotine antibody derived from the Fab fragment of the anti-nicotine monoclonal antibody NIC9D9 (AAVantiNic). In mice treated with this vector, blood concentrations of the anti-nicotine antibody were dose-dependent, and the antibody showed high specificity and affinity for nicotine. The antibody shielded the brain from systemically administered nicotine, reducing brain nicotine concentrations to 15% of those in naïve mice. The amount of nicotine sequestered in the serum of vector-treated mice was more than seven times greater than that in untreated mice, with 83% of serum nicotine bound to immunoglobulin G. Treatment with the AAVantiNic vector blocked nicotine-mediated alterations in arterial blood pressure, heart rate, and locomotor activity. In summary, a single administration of a gene transfer vector expressing a high-affinity anti-nicotine monoclonal antibody elicited persistent (18 weeks), high titers of an anti-nicotine antibody that obviated the physiologic effects of nicotine. If this degree of efficacy translates to humans, AAVantiNic could be an effective preventative therapy for nicotine addiction.
DOI	10.1126/scitranslmed.3003611
PubMed ID	22745437
PubMed Central ID	PMC3622954