A therapeutic vaccine for nicotine dependence: preclinical efficacy, and Phase I safety and immunogenicity

Eur J Immunol. 2005 Jul;35(7):2031-40. doi: 10.1002/eji.200526285.

Abstract

Nicotine is the principal addictive component in tobacco, and following uptake acts in the central nervous system. The smoking-cessation efforts of most smokers fail because a single slip often delivers sufficient nicotine to the brain to reinstate the drug-seeking behaviour. Blocking nicotine from entering the brain by induction of specific antibodies may be an effective means to prevent such relapses. The hapten nicotine was coupled to virus-like particles (VLP) formed by the coat protein of the bacteriophage Qb. In preclinical experiments, this Nicotine-Qb VLP (NicQb) vaccine induced strong antibody responses. After intravenous nicotine challenge, vaccinated mice exhibited strongly reduced nicotine levels in the brain compared with control mice. In a phase I study, 32 healthy non-smokers were immunized with NicQb. The vaccine was safe and well-tolerated. All volunteers who received NicQb showed nicotine-specific IgM antibodies at day 7 and nicotine-specific IgG antibodies at day 14. Antibody levels could be boosted by a second injection or the addition of Alum as an adjuvant and the antibodies had a high affinity for nicotine. These data suggest that antibodies induced by NicQb may prevent relapses by sequestering nicotine in the blood of immunized smokers.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Allolevivirus / genetics
  • Allolevivirus / immunology
  • Animals
  • Double-Blind Method
  • Drug Evaluation, Preclinical
  • Female
  • Humans
  • Immunoglobulin G / biosynthesis*
  • Male
  • Mice
  • Middle Aged
  • Nicotine / immunology*
  • Tobacco Use Disorder / immunology*
  • Tobacco Use Disorder / prevention & control*
  • Vaccines / administration & dosage*
  • Vaccines / adverse effects
  • Vaccines / genetics
  • Vaccines / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / adverse effects
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • Immunoglobulin G
  • Vaccines
  • Vaccines, Synthetic
  • Nicotine