Abstract
In contrast to current pharmacotherapies, immunologic approaches to treating tobacco dependence target the drug itself rather than the brain. This approach involves the use of nicotine-specific antibodies that bind nicotine in serum, resulting in a decrease in nicotine distribution to the brain and an increase in nicotine’s elimination half-life. This review summarizes the literature examining the effects of immunologic interventions on the pharmacokinetics and behavioral effects of nicotine in animal models, as well as recent phase I and II clinical trials in humans. Studies using various vaccines and nicotine-specific antibodies in rodents have shown that immunization can significantly reduce the behavioral effects of nicotine that are relevant to tobacco dependence (eg, nicotine self-administration). These findings provide proof of principle that immunologic interventions could have utility in the treatment of tobacco dependence. Thus far, phase I clinical trials of nicotine vaccines have not produced any serious adverse events in humans and have produced dose-dependent increases in serum antibody levels. Although preliminary data from these small trials suggest that vaccination can facilitate abstinence from tobacco use, more advance trials are needed. By acting outside the nervous system, immunologic approaches are less likely to produce the adverse side effects associated with current medications. In addition, the unique mechanism of action of immunotherapy makes it particularly suitable for combination with other pharmacological approaches. Taken together, the work completed to date provides substantial evidence that immunologic interventions could play an important role in future treatment strategies for tobacco dependence.
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References
Centers for Disease Control and Prevention (CDC). Annual smoking-attributable mortality, years of potential life lost, and economic costs-United States, 1995-1999. MMWR Morb Mortal Wkly Rep. 2002;51:300-303.
U. S. Department of Health and Human Services. Healthy People 2010. With understanding and improving health and objectives for improving health. Washington, DC: US Department of Health and Human Services; 2000.
Harvey DM, Yasar S, Heishman SJ, Panlilio LV, Henningfield JE, Goldberg SR. Nicotine serves as an effective reinforcer of intravenous drug-taking behavior in human cigarette smok-ers. Psychopharmacology (Berl). 2004;175:134-142.
Stolerman IP, Jarvis MJ. The scientific case that nicotine is addictive. Psychopharmacology (Berl). 1995;117:2-10. Discussion 14-20.
Corrigall WA. Nicotine self-administration in animals as a dependence model. Nicotine Tob Res. 1999;1:11-20.
Gerrits MA, Petromilli P, Westenberg HG, Di Chiara G, van Ree JM. Decrease in basal dopamine levels in the nucleus accumbens shell during daily drug-seeking behaviour in rats. Brain Res. 2002;924:141-150.
Wonnacott S, Sidhpura N, Balfour DJ. Nicotine: from molecular mechanisms to behaviour. Curr Opin Pharmacol. 2005;5:53-59.
Fiore MC. US public health service clinical practice guideline: treating tobacco use and dependence. Respir Care. 2000;45:1200-1262.
Ferry L, Johnston JA. Efficacy and safety of bupropion SR for smoking cessation: data from clinical trials and five years of postmarketing experience. Int J Clin Pract. 2003;57:224-230.
Fiore MC, Smith SS, Jorenby DE, Baker TB. The effectiveness of the nicotine patch for smoking cessation: a meta-analysis. JAMA. 1994;271:1940-1947.
Hurt RD, Sachs DP, Glover ED, et al. A comparison of sustained-release bupropion and pla-cebo for smoking cessation. N Engl J Med. 1997;337:1195-1202.
Haney M, Kosten TR. Therapeutic vaccines for substance dependence. Expert Rev Vaccines. 2004;3:11-18.
Pentel PR, Keyler DE. Vaccines to treat drug addiction. In: Levine MM, Kaper JB, Rappuoli R, Liu MA, Good MF, eds. New Generation Vaccines. New York, NY: Marcel Dekker; 2004.
Goldberg SR, Spealman RD. Suppression of behavior by intravenous injections of nicotine or by electric shocks in squirrel monkeys: effects of chlordiazepoxide and mecamylamine. J Pharmacol Exp Ther. 1983;224:334-340.
Benowitz NL, Perez-Stable EJ, Herrera B. Jacob Pr. Slower metabolism and reduced intake of nicotine from cigarette smoking in Chinese-Americans. J Natl Cancer Inst. 2002;94:108-115.
Malaiyandi V, Sellers EM, Tyndale RF. Implications of CYP2A6 genetic variation for smok-ing behaviors and nicotine dependence. Clin Pharmacol Ther. 2005;77:145-158.
Schoedel KA, Hoffmann EB, Rao Y, Sellers EM, Tyndale RF. Ethnic variation in CYP2A6 and association of genetically slow nicotine metabolism and smoking in adult Caucasians. Pharmacogenetics. 2004;14:615-626.
Hieda Y, Keyler DE, Vandevoort JT, et al. Active immunization alters the plasma nicotine concentration in rats. J Pharmacol Exp Ther. 1997;283:1076-1081.
de Villiers SH, Lindblom N, Kalayanov G, et al. Active immunization against nicotine sup-presses nicotine-induced dopamine release in the rat nucleus accumbens shell. Respiration. 2002;69:247-253.
Carrera MR, Ashley JA, Hoffman TZ, et al. Investigations using immunization to attenuate the psychoactive effects of nicotine. Bioorg Med Chem. 2004;12:563-570.
Sanderson SD, Cheruku SR, Padmanilayam MP, et al. Immunization to nicotine with a peptide-based vaccine composed of a conformationally biased agonist of C5a as a molecular adjuvant. Int Immunopharmacol. 2003;3:137-146.
Cerny EH, Levy R, Mauel J, et al. Preclinical development of a vaccine “against smoking.” Onkologie. 2002;25:406-411.
Pentel PR, Malin DH, Ennifar S, et al. A nicotine conjugate vaccine reduces nicotine distribu-tion to brain and attenuates its behavioral and cardiovascular effects in rats. Pharmacol Biochem Behav. 2000;65:191-198.
Maurer P, Jennings GT, Willers J, et al. A therapeutic vaccine for nicotine dependence: preclini-cal efficacy, and Phase I safety and immunogenicity. Eur J Immunol. 2005;35:2031-2040.
LeSage MG, Keyler DE, Hieda Y. Effects of a nicotine conjugate vaccine on the acquisition and maintenance of nicotine self-administration in rats. Psychopharmacology (Berl). 2005;1-8.
Meijler MM, Jr, Matsushita M, Jr, Altobell L, Jr, Wirsching P, Janda KD. A new strategy for improved nicotine vaccines using conformationally constrained haptens. J Am Chem Soc. 2003;125:7164-7165.
St Clair Roberts J, Akers CVR, Vanhinsbergh L, McKenna KA, Wood DM, Jack L. Longitudinal safety and immunogenicity data of TA-NIC, a novel nicotine vaccine. Proceedings of the Ninth Annual Meeting of the Society for Research on Nicotine and Tobacco Ninth Annual Meeting of the Society for Research on Nicotine and Tobacco; February 19-22, 2003; New Orleans, LA. Middletown, WI: Society for Research on Nicotine and Tobacco; 2003.
Hatsukami D, Rennard S, Jorenby DE, et al. Safety and immunogenicity of a nicotine conju-gate vaccine in current smokers. Clin Pharmacol Ther. 2005;78:456-467.
St Clair Roberts J, Dobson J, Wood D, Settles M. Safety and immunogenicity of a human nic-otine conjugate vaccine. Drug Alcohol Depend. 2002;66:S148.
Keyler DE, Roiko SA, Benlhabib E, et al. Monoclonal nicotine-specific antibodies reduce nicotine distribution to brain in rats: dose- and affinity-response relationships. Drug Metab Dispos. 2005;33:1056-1061.
Malin DH, Lake JR, Lin A, et al. Passive immunization against nicotine prevents nicotine alleviation of nicotine abstinence syndrome. Pharmacol Biochem Behav. 2001;68:87-92.
de Villiers SH, Lindblom N, Kalayanov G, Gordon S, Johansson AM, Svensson TH. Active immunization against nicotine alters the distribution of nicotine but not the metabolism to cotinine in the rat. Naunyn Schmiedebergs Arch Pharmacol. 2004;370:299-304.
Satoskar SD, Keyler DE, LeSage MG, Raphael DE, Ross CA, Pentel PR. Tissue-dependent effects of immunization with a nicotine conjugate vaccine on the distribution of nicotine in rats. Int Immunopharmacol. 2003;3:957-970.
Perkins KA, Jacobs L, Sanders M, Caggiula AR. Sex differences in the subjective and rein-forcing effects of cigarette nicotine dose. Psychopharmacology (Berl). 2002;163:194-201.
Keyler DE, Hieda Y, St Peter J, Pentel PR. Altered disposition of repeated nicotine doses in rats immunized against nicotine. Nicotine Tob Res. 1999;1:241-249.
Hieda Y, Keyler DE, Ennifar S, Fattom A, Pentel PR. Vaccination against nicotine during continued nicotine administration in rats: immunogenicity of the vaccine and effects on nico-tine distribution to brain. Int J Immunopharmacol. 2000;22:809-819.
Keyler DE, Dufek MB, Calvin AD, et al. Reduced nicotine distribution from mother to fetal brain in rats vaccinated against nicotine: time course and influence of nicotine dosing regimen. Biochem Pharmacol. 2005;69:1385-1395.
Stolerman IP. Interspecies consistency in the behavioural pharmacology of nicotine depend-ence. Behav Pharmacol. 1999;10:559-580.
Tuncok Y, Hieda Y, Keyler DE, et al. Inhibition of nicotine-induced seizures in rats by com-bining vaccination against nicotine with chronic nicotine infusion. Exp Clin Psychopharmacol. 2001;9:228-234.
Shiffman S, West R, Gilbert D. Recommendation for the assessment of tobacco craving and withdrawal in smoking cessation trials. Nicotine Tob Res. 2004;6:599-614.
Malin DH, Alvarado CL, Woodhouse KS, et al. Passive immunization against nicotine attenu-ates nicotine discrimination. Life Sci. 2002;70:2793-2798.
Lindblom N, de Villiers SH, Kalayanov G, Gordon S, Johansson AM, Svensson TH. Active immunization against nicotine prevents reinstatement of nicotine-seeking behavior in rats. Respiration. 2002;69:254-260.
Keyler DE, Shoeman D, LeSage MG, Calvin AD, Pentel PR. Maternal vaccination against nico-tine reduces nicotine distribution to fetal brain in rats. J Pharmacol Exp Ther. 2003;305:587-592.
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LeSage, M.G., Keyler, D.E., Pentel, P.R. (2008). Current Status of Immunologic Approaches to Treating Tobacco Dependence: Vaccines and Nicotine-Specific Antibodies. In: Rapaka, R.S., Sadée, W. (eds) Drug Addiction. Springer, New York, NY. https://doi.org/10.1007/978-0-387-76678-2_27
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