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 welltolerated. 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.

Delivery strategies to enhance oral vaccination against enteric infections

“…Additionally, this multimeric complex lacks any viral RNA/DNA and is therefore incapable of replication [168]. Moreover, VLPs can be expressed with additional antigens on or, in the case of polysaccharide or lipid molecules, conjugated to the surface to create a multivalent vaccine [166,[169][170][171]. VLPs contain one or more viral capsid proteins which make up the protective outer shell of a virion and are usually expressed in a eukaryotic cell [110].…”

Vaccination against IL‐17 suppresses autoimmune arthritis and encephalomyelitis

“…We have previously demonstrated that highly ordered and repetitive display of antigens on the surface of VLP can induce strong and long lasting B cell responses in mice and humans [28,29]. Hence, it is possible to induce antibodies against self-antigens without the addition of further adjuvants [26,28].…”

Therapeutic vaccines for chronic diseases: successes and technical challenges

“…To successfully neutralize haptens or endogenous small and large soluble polypeptides such as these, it is essential to induce sufficient amounts of high-affinity antibodies. For instance, our current experience indicates that for vaccination against nicotine to be successful, it is necessary to attain levels of nicotine-specific IgG of 10 mg ml [3]. This is orders of magnitude higher than what is usually required for protection against viral infection.…”

“…This can be achieved by active vaccination, which induces anti-nicotine antibodies that act to prevent reinstatement of the positive reinforcement resulting from relapse. Proof of concept for this approach has been achieved in animals [3,24]. The mechanism for this is relatively simple.…”

“…To study the immunogenicity of this vaccine, non-smoking human volunteers were immunized twice with 50 or 100 mg of NicQb in saline [3]. The higher dose was also formulated in alum.…”