title: A therapeutic vaccine for nicotine dependence: preclinical efficacy, and Phase I safety and immunogenicity.
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.
authors.affiliation: Cytos Biotechnology AG, Zürich, Switzerland.
authors.forename: Patrik
authors.initials: P
authors.lastname: Maurer
authors.forename: Gary T
authors.initials: GT
authors.lastname: Jennings
authors.forename: Jörg
authors.initials: J
authors.lastname: Willers
authors.forename: Franziska
authors.initials: F
authors.lastname: Rohner
authors.forename: Ylva
authors.initials: Y
authors.lastname: Lindman
authors.forename: Kirsten
authors.initials: K
authors.lastname: Roubicek
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Renner
authors.forename: Philipp
authors.initials: P
authors.lastname: Müller
authors.forename: Martin F
authors.initials: MF
authors.lastname: Bachmann
mesh_terms: D000293:Adolescent; D000328:Adult; D017908:Allolevivirus / Q000235:genetics / Q000276:immunology; D000818:Animals; D004311:Double-Blind Method; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009538:Nicotine / Q000276:immunology*; D014029:Tobacco Use Disorder / Q000276:immunology* / Q000517:prevention & control*; D014612:Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; D014612:Vaccines; D014614:Vaccines, Synthetic; D009538:Nicotine