Abstract and Introduction
Despite significant reductions over the past 45 years in the percentage of individuals smoking cigarettes, tobacco-related illnesses remain the leading cause of preventable death in the United States. Although the health risks of tobacco use have been clearly outlined, addiction to nicotine traditionally has been one of the more challenging habits to break. Seven first-line therapies to treat tobacco use and dependence are available; however, annual quit rates remain surprisingly low, suggesting that continued research and development in the area of smoking cessation are warranted. In an attempt to improve long-term quit rates and blunt the reinforcing effects of nicotine in the brain, the nicotine conjugate vaccine was developed as a novel approach for the treatment of nicotine dependence. Vaccine administration produces nicotine-specific antibodies that bind to nicotine from exogenous sources, creating a large unit that is not able to cross the blood-brain barrier, which limits the rate and extent of nicotine absorption into the brain. Results of clinical trials indicate that individuals achieving high nicotine-specific antibody levels with the nicotine conjugate vaccine have greater success with smoking cessation at 12 months compared with those with lower levels. Adverse effects associated with the nicotine conjugate vaccine have been primarily mild and localized in nature, with minimal systemic effects. The most commonly reported adverse effects include tenderness and ache at the injection site, general discomfort, headache, and muscle ache. Awaiting results of phase III trials, the true clinical utility of the nicotine conjugate vaccine is yet to be realized, although this investigational vaccine represents a distinctive administration model that may improve patient adherence and increase the ability to achieve abstinence from cigarette smoking.
Despite significant reductions over the past 45 years in the percentage of individuals smoking cigarettes in the United States, tobacco-related illnesses remain the leading cause of preventable death, killing approximately 443,000 individuals annually.[1,2] Estimates from 2009 indicate that 20.6% of U.S. adults are smokers, a percentage that has remained relatively unchanged over the past 6 years and still significantly above the Healthy People 2010 goal of 12%. Simulation models indicate that if no progress is made in reducing smoking initiation and increasing success with cessation attempts, smoking rates in the United States will level off at 13.5% around the middle of the century. Globally, tobacco is responsible for over 5 million deaths every year, with developing countries at substantially higher risk than developed countries. Highlighting the urgency of the tobacco epidemic worldwide, tobacco is expected to be accountable for over a billion deaths by the end of the century unless immediate widespread action is taken.
Although the health risks of tobacco use have been clearly outlined, addiction to nicotine traditionally has been one of the more challenging habits to break. The development of the cigarette as a nicotine delivery device allows nicotine to reach the brain within seconds of inhalation, stimulating multiple reward pathways and neurotransmitters, including dopamine, serotonin, norepinephrine, vasopressin, glutamate, γ-aminobutyric acid, and β-endorphins. Individual response to nicotine varies widely based on genetic determinants and environmental factors, with research indicating that the younger an individual starts smoking, the more highly dependent the person is likely to become.
Drug therapies to assist individuals interested in smoking cessation were first introduced on the market with the nicotine gum in 1984. Seven first-line therapies—nicotine gum, nicotine patch, nicotine lozenge, nicotine nasal spray, nicotine inhaler, bupropion, and varenicline—are endorsed by the most recent publication of the U.S. Department of Health and Human Services guidelines for treating tobacco use and dependence. Varenicline, a partial agonist that both stimulates and blocks binding sites for nicotine in the brain, was the last smoking-cessation drug approved by the U.S. Food and Drug Administration. Despite improved success with these therapies, annual quit rates remain surprisingly low (< 10% remain abstinent at 1 yr), suggesting that continued research and development in the area of smoking cessation are warranted.
In an attempt to improve long-term quit rates and blunt the reinforcing effects of nicotine in the brain, the nicotine conjugate vaccine (NicVAX [3′-aminomethylnicotine conjugated to recombinant Pseudomonas exoprotein A (3′-AmNic-rEPA)]; Nabi Biopharmaceuticals, Rockville, MD) was developed as a novel approach to the treatment of nicotine dependence. The 3′-AmNic-rEPA vaccine represents one of four nicotine vaccines under investigation in humans; it is the furthest along in clinical trials. Although termed a vaccine, 3′-AmNic-rEPA more closely represents immunotherapy, with the intention of reducing the rate and extent of nicotine absorp-tion into the brain, rather than offering complete, lifetime protection from the effects of a cigarette.
To gain a better understanding of the safety and efficacy of the 3′-AmNic-rEPA vaccine, an English-language literature search of the PubMed database from 1966–January 2011 was performed by using the search terms NicVAX, nicotine conjugate vaccine, nicotine vaccine, and tobacco cessation. Publications that discussed the pharmacokinetics, safety, and efficacy of the 3′-AmNic-rEPA vaccine for smoking cessation were selected to undergo further evaluation. References from the selected articles were used to identify other pertinent trials. Additional information available from the manufacturer was included in the review. The national clinical trials Web site (www.clinicaltrials.gov) was accessed to identify previous and ongoing studies involving the 3′-AmNic-rEPA vaccine.
Pharmacotherapy. 2011;31(7):703-713. © 2011 Pharmacotherapy Publications
Cite this: Nicotine Conjugate Vaccine as a Novel Approach to Smoking Cessation - Medscape - Jul 01, 2011.