A nicotine vaccine may be an effective method for preventing and treating tobacco addiction, according to a new study funded in part by the National Institute on Drug Abuse (NIDA), National Institutes of Health.

Researchers associated with the Minneapolis Medical Research Foundation and Hennepin County Medical Center; the University of Houston-Clear Lake; and Nabi, a pharmaceutical firm based in Boca Raton, Florida, have developed a nicotine vaccine consisting of a nicotine derivative attached to a large protein, according to findings published in the December 17 issue of Pharmacology, Biochemistry and Behavior. Nicotine is the main addictive component of tobacco. The purpose of the vaccine is to prevent nicotine from reaching the brain so as to reduce its effects and help keep people from becoming addicted. "A nicotine vaccine may be useful for preventing and treating tobacco addiction because vaccinated persons would not be able get a 'kick' from the nicotine in tobacco smoke or chewing tobacco," says NIDA Director Dr. Alan I. Leshner. "Since they would find tobacco less rewarding, they would be less likely to continue using it." He added that NIDA is also supporting efforts to produce vaccines directed against cocaine, methamphetamine, and PCP. When injected in laboratory animals, the vaccine stimulates the immune system to produce proteins called antibodies that bind tightly to nicotine. The antibody-bound nicotine is too large to enter the brain, thereby preventing nicotine from producing its effects. The antibody-bound nicotine is eventually broken down to other harmless molecules. The scientists injected a single dose of nicotine into vaccinated rats and found that the amount of nicotine reaching the brain was reduced by 64%. They also administered various doses of antibodies to the rats and studied how the antibodies affected nicotine's tendency to raise blood pressure and stimulate movement. The researchers found that administering doses of nicotine antibodies similar to those that are ordinarily produced by the vaccine greatly reduced the rise in blood pressure produced by a nicotine injection. The antibodies also completely prevented the increased movements ordinarily seen when rats are injected with nicotine. The lead author of the article, Dr. Paul Pentel, says that a nicotine vaccine should be less likely to produce side effects than medications that act in the brain to counter nicotine's effects because the vaccine itself never enters the brain. "Nicotine is a particularly good candidate for a vaccine because it is a very potent drug. The doses of nicotine that people need to feel its effects are relatively small, so that the antibodies produced by vaccination can bind a large fraction of each nicotine dose," says Dr. Pentel. Study co-author Dr. David Malin points out that, "Vaccines can have very long-lasting effects. This may be helpful because smokers who quit sometimes relapse and resume smoking weeks or months later." "We are encouraged by the results obtained so far in these studies," says Dr. Pentel. The next steps will be to conduct additional safety studies, followed by clinical trials with the vaccine in human volunteers. These clinical trials are currently scheduled to be coordinated by Nabi Pharmaceuticals beginning in early 2002.

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