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

Overview

MeSH

  • Animals
  • Male
  • Mice
  • Mice, Inbred C57BL

MeSH Major

  • 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 na├»ve 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.

publication date

  • June 27, 2012

has subject area

  • Animals
  • Antibodies, Monoclonal
  • Dependovirus
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nicotine
  • Smoking Cessation

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3622954

Digital Object Identifier (DOI)

  • 10.1126/scitranslmed.3003611

PubMed ID

  • 22745437

Additional Document Info

start page

  • 140ra87

volume

  • 4

number

  • 140