Vaccines to combat smoking

Abstract

Background: Current US FDA-approved biological therapies for treating smoking target central nervous system processes. Although these therapies have had some success, relapse within a year is still high. Clearly additional strategies are needed to aid individuals in maintaining abstinence.

Objective/methods: We briefly discuss promising research using vaccines to combat smoking and then identify some potentially important directions for future research.

Results/conclusions: Immunization with a nicotine vaccine generates drug-specific antibodies that sequester some of the nicotine in the peripheral circulation preventing it from entering the brain, thus decreasing its addictive effects. Albeit promising, much more research is necessary to identify more efficacious vaccine designs and formulations, as well as optimal immunization regimens. A further understanding of the factors contributing to the substantial individual differences in immunogenicity to these vaccines and how to best use vaccines in combination with other treatment strategies will increase the success of intervention efforts.

Figure 1

This cartoon diagrams the rationale and mechanism behind a vaccine for the treatment of nicotine use (e.g., smoking). An individual is vaccinated according to some empirically determined immunization schedule. Immunization with the nicotine vaccine will activate the immune system to produce drug-specific antibodies. If an immunized individual then uses a nicotine-containing product such as cigarettes, some portion of the nicotine in serum and extracellular fluid will be sequestered by the antibodies. Although nicotine readily passes through the blood-brain-barrier, antibodies are too large to do so resulting in less nicotine entering the brain. This decreases nicotine’s impact on brain systems involved in addiction (e.g., mesocorticolimbic system). Especially effective vaccines will be ones that raise a robust immune response with the fewest immunization boosts, produce antibodies that are highly specific for nicotine, and include a binding affinity that allows the initial introduction of nicotine into the periphery to be sequestered very quickly.