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

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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.