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By Cindy Won, '20  Smoking remains the leading preventable cause of death in the United States. We see everywhere in medical headlines that diseases such as cancer and diabetes are some of the leading causes of death. But what really drives the high prevalence of these conditions? In reality, smoking is the leading cause of preventable death in the United States. Ever since the Surgeon General Report of 1964 revealed the deleterious effects of smoking on various organs in the body, tobacco prevention strategies have been implemented in public health education. Despite these strategies, over 42 million continue to smoke [1], and smoking is responsible for more than 480,000 deaths in the United States, both directly and indirectly  So what is it about tobacco that makes one want to continue smoking, despite its claimed toxicity? Simple: nicotine. An organic chemical compound that mirrors the neurotransmitter acetylcholine, nicotine is absorbed very quickly into the bloodstream and stimulates the parasympathetic nervous system by pretending to be acetylcholine. It then activates receptors in the brain that increases the levels of dopamine, a neurotransmitter in the body that controls the reward and pleasure centers of the brain [2]. With continuous stimulation and activation of receptors, the body becomes increasingly tolerized to the amounts of nicotine and requires increasing quantities. Subsequent exposures with greater quantities of nicotine leads to what is commonly understood as addiction. Cigarettes, unfortunately, are an incredibly efficient nicotine delivery vehicle.
Due to the addictive nature of nicotine and its effective delivery via cigarettes, a variety of nicotine dependence interventions have focused on changing its delivery route. One particular semi-successful approach is nicotine replacement therapy. From nicotine patches to nicotine gum, these products aim to deliver nicotine in smaller dosages and help mediate the effects of withdrawal. While these have been proven to increase the chances of quitting smoking, the possibility of continued addiction to smoking is not completely guaranteed. A new immunological approach is to generate an antibody response to the nicotine in order to prevent the nicotine from activating the receptors associated with the parasympathetic nervous system. One of the specific characteristics of nicotine is that it can serve as a hapten. A hapten is an organic chemical molecule that, when in the body, does not generate any immune response. In this context, when an immune response is generated, the body generates antibodies that neutralize this foreign compound. Figure 1. A general summary of the effects of haptens and its carrier molecules in generating antibody responses (Taken from slideshare.net) Recently, researchers have been exploring the possibility of developing an anti-nicotine vaccine which would link the nicotine to another larger carrier molecule. This carrier molecule will induce the creation of antibodies specific to the nicotine. A recent study conducted by the Scripps Department of Chemistry and Immunology investigated the usage of nicotine-like haptens in anti-nicotine vaccines [3]. The premise of the study was to generate antibodies to the nicotine-carrier molecule so that they can neutralize the nicotine before it reaches the receptors. Overall, this study demonstrated delays in the effects of nicotine on mice and the potential to be used as a therapy for nicotine relapse. Though the vaccine offers promising results and a variety of possibilities for the future, there are a variety of risks and variables that need to be accounted for. For instance, there is the concern of whether the antibodies specific to the nicotine would be generated from memory faster than the rate at which the nicotine binds to its specific receptors in the brain. If the nicotine reached these receptors faster than the antibodies could neutralize them, then the antibody response would not be effective. There is also the strong possibility that even though an antibody response is generated, the antibodies present are not protective. Complications are not just limited to the molecular mechanism; the vaccine itself, the route of administration, and which types of carrier proteins will be linked to the nicotine in order to generate the response. According to the study “Nicotine hapten structure, antibody specificity, etc”, the types of molecules that were used to link the nicotine and the carrier protein together would change the number of antibodies that were generated [4]. The most optimal combination would have to be tested on a variety of the population and thus slow down the production of the anti-nicotine vaccines. Furthermore, an individual may react to the vaccine in an adverse reaction, leading to exclusion of subsets of the population. How do we move forward, even though more than 8.5% of deaths are caused by secondhand smoke by itself? How do we move forward in an increasingly neoliberal society, in which these types of therapies and vaccinations are becoming “supplements” instead of necessities? How do we continue to move forward in a world in which e-cigarettes are now being used in lieu of actual cigarettes and nicotine is still being ingested left and right in unhealthy amounts? This definitely is a feat that will take time and consideration for the shifts in the culture of the society we live in. However, the current development of the anti-nicotine vaccine and the research behind the immunological responses show promise for those who are struggling within this epidemic. Citations (1) American Academy of Family Physicians. Tobacco: Preventing and Treating Nicotine Dependence and Tobacco Use. AAFP https://www.aafp.org/about/policies/all/nicotine-tobacco-prevention.html#Introduction (2) BeTobaccoFree.gov. Nicotine Addiction and Your Health. Department of Health and Human Services. https://betobaccofree.hhs.gov/health-effects/nicotine-health/index.html (3) Jacob, Nicholas T., Lockner, Jonathan W.; Schlosburg, Joel E.; Ellis, Beverly A; Eubanks, Lisa M.; Janda, Kim D. Investigations of Enantiopure Nicotine Haptens Using an Adjuvanting Carrier in Anti-Nicotine Vaccine Development. Journal of Medicinal Chemistry, 2016, 59 (6), 523-2529. https://dx.doi.org/10.1021/acs.jmedchem.5b01676 (4) de Villiers, SH; Lindblom, N.; Kalayanov, G; Gordon, S. Nicotine hapten structure, antibody selectivity and effect relationships: results from a nicotine vaccine screening procedure. Vaccine, 2010, 59 (10), 2161-8. https://dx.doi.org/10.1016/j.vaccine.2009.12.051
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