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Conformationally constrained nicotine vaccines

Institution: Scripps Research Institute
Investigator(s): Kim Janda, Ph.D.
Award Cycle: 2005 (Cycle 14) Grant #: 14RT-0110 Award: $778,921
Subject Area: Nicotine Dependence
Award Type: Research Project Awards

Initial Award Abstract
Tobacco abuse is an extremely significant problem in modern society. Although scientists are aware of the negative effect nicotine exposure has on a person’s health, many people continue to smoke and suffer from a variety of illnesses resulting from tobacco exposure. It is estimated that 51 million Americans smoke, and that smoking causes approximately 419,000 deaths per year in the United States alone, making it the leading cause of preventable death.

The two most popular therapies for smoking abatement are nicotine gum and transdermal nicotine patches. However, poor success rates have been observed with either of these methods. As a result, it is important to try and develop new methods to help people quit smoking that have higher rates of success. One approach to this problem is the development of antibodies that could absorb the nicotine from a person’s bloodstream and then remove it from the body before it is able to produce any addictive effects. This technique has had success previously in cocaine abuse and we believe it has potential implications in tobacco abuse as well. These antibodies would prevent the nicotine from reaching a smoker’s brain and thus prevent the addiction. This method, along with other therapies aimed at treating the psychological effect of nicotine addiction, such as counseling, could help people who are addicted to nicotine.

Other research groups have tried to develop vaccines that could help treat nicotine addiction, with all studies focusing on vaccines that greatly resemble the nicotine molecule. However, nicotine is a flexible molecule. Only one specific shape of nicotine is biologically active, thus any antibodies against nonactive structures are not useful. We have found that by forcing the nicotine molecule into only one shape, we can achieve a much better antibody response than previous studies. Our proposal is designed to explore this phenomenon and characterize the ability of these antibodies to protect against the negative effects of nicotine. We will perform our studies in an animal model as an alternative to performing experiments directly in humans. Our laboratory has extensive experience in performing animal testing in a safe and humane manner. In total, our studies will provide a novel perspective into nicotine addiction treatment and may eventually lead to an effective vaccine that would help prevent the vast number of preventable deaths caused by smoking.