A new vaccine that prevents nicotine from reaching the brains of rats may offer hope for smokers trying to break their addiction. The compound, called NicVAX, may even prove useful as an inoculation against nicotine addiction, much like those that protect children from tetanus, measles, and polio.

"Some form of vaccination against nicotine would be highly useful because vaccinated individuals would not be able to get a 'kick' from the nicotine in tobacco smoke or chewing tobacco," says NIDA Director Dr. Alan I. Leshner. "If people found tobacco less rewarding, they would be less likely to continue using it. Ultimately, however, our best treatment for nicotine addiction is prevention."

NicVAX is manufactured by Nabi, a Florida-based pharmaceutical company that has NIDA grant support to conduct preclinical studies to determine whether the vaccine is toxic to animals and, then, if the compound is proven safe, clinical trials to evaluate its safety and efficacy in humans. The 4-year project begins this fall, and clinical trials are planned for 2002. Primary coinvestigators include Dr. Ali Fattom and other Nabi scientists in Rockville, Maryland, as well as the Minnesota- and Texas-based researchers who conducted the early animal studies.

Dr. Ali Fattom (left) and Dr. Sham Shirali of Nabi examine a flask of the nicotine preparation used to produce NicVAX. Photo by Jane Barrett, Nabi, Rockville, Maryland.

Dr. Paul Pentel and his colleagues at the Minneapolis Research Foundation and Hennepin County Research Center in Minneapolis and Dr. David Malin at the University of Houston at Clear Lake tested NicVAX with rats. Injection of NicVAX stimulated antibodies to neutralize nicotine in the blood, reducing by 65 percent the amount of nicotine that reached the animals' brains. The nicotine-specific antibodies produced by NicVAX also reduced the effects of nicotine on blood pressure and the heart.

Now NicVAX is proposed as a therapy that can enhance current treatments for nicotine addiction by helping quitting smokers resist the urge to light up. The hypothesis is that the vaccine may inhibit nicotine's "priming effect"-the phenomenon in which a formerly addicted individual experiences an increased desire to use a drug after a single exposure, which contributes to relapse. A treatment program built around NicVAX might also include supportive counseling and a medication such as bupropion (Zyban) to reduce withdrawal symptoms.

The animal studies suggest the vaccine's potential for preventing addiction in new tobacco users as well. When rats were injected simultaneously with a nicotine solution and the vaccine, the antibodies that reduced nicotine levels in the rat brains also reduced nicotine dependence. When the nicotine dosing was stop-ped, the control group, rats injected with nicotine and a placebo solution, showed significantly greater levels of dependence-measured by abstinence signs such as teeth chattering and tremors-than did the rats treated with NicVAX. Rats were exposed to nicotine at levels comparable to 10 packs of cigarettes daily for a week.

Continuing doses of nicotine do not interfere with the vaccine's ability to induce antibodies in the rats. Animals immunized with NicVAX while they were being injected with nicotine still produced nicotine-specific antibodies. Thus it may be possible to vaccinate a smoker while he or she is still using tobacco so that adequate antibodies will be in place at smoking cessation. The vaccine will continue to work during any relapse, inhibiting the pleasurable response that nicotine would otherwise cause. Further, the vaccine never enters the brain and is therefore unlikely to produce neurological side effects.

Sources

Pentel, P.R.; Malin, D.H.; Ennifar, S.; et al. A nicotine conjugate vaccine reduces nicotine distribution to brain and attenuates its behavioral and cardiovascular effects in rats. Pharmacology Biochemistry and Behavior 65(1): 191-198, 1999.[Abstract]

Hieda, Y.; Keyler, D.E.; VanDeVoort, J.T.; et al. Immunization of rats reduces nicotine distribution to brain. Psychopharmacology 143: 150-157. [Full Text]