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

Journal article

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.

Authors: Maurer, P; Jennings, G; Willers, J; Rohner, F; Lindman, Y

• Publication status: Published
• Journal: European journal of immunology
• Volume: 35
• Issue: 7
• Pages: 2031-2040
• Publication date: 2005-07-01
• DOI: 10.1002/eji.200526285
• EISSN: 1521-4141
• ISSN: 0014-2980
• Language: English
• Keywords: Middle Aged; Adult; Male; Tobacco Use Disorder; Immunoglobulin G; Mice; Adolescent; Nicotine; Double-Blind Method; Vaccines, Synthetic; Vaccines; Allolevivirus; Animals; Female; Humans; Drug Evaluation, Preclinical