Pulse
A Shot at Quitting
New vaccine is a shot in the arm for smokers trying to quit.
Can a simple shot prevent tobacco addiction? Probably not. But University of Minnesota researchers are finding that a new nicotine vaccine, NicVAX, may help adults who already smoke abstain from cigarettes.
Unlike vaccines for diseases such as measles and mumps, which are administered during childhood and protect people from devastating illnesses for years, NicVAX appears to work more like a medication that needs to be given in multiple doses.
“With infectious diseases, you get vaccinated, and get long-lasting, near complete protection. That is not the case with vaccines for nicotine, where the effects are much more analogous to those of medications,” says Paul Pentel, M.D., a University of Minnesota professor of pharmacology, who conducted NicVAX animal trials.
Pentel explains that the immune system responds differently to nicotine than it does to bacteria or a virus because nicotine molecules by themselves are too small to trigger an immune response.
How It Works
The vaccine, nicotine molecules combined with larger proteins, stimulates the body’s immune system to produce antibodies that can bind to nicotine when the person smokes. The antibody-bound nicotine molecules are too big to pass from the blood into the brain, thus reducing or slowing the entry of nicotine to the brain and blunting its pleasurable effect.
“Slower delivery of nicotine to the brain turns out to be very important because the rewarding effects of drugs are related to how fast they enter the brain,” Pentel says, adding that his laboratory found that rats pressed a lever for nicotine less frequently after being vaccinated.
Pentel says the antibodies also have a limited lifespan of one to two months and that smokers will likely need booster shots of the vaccine every two to six months in order to prompt the immune system to produce new antibodies and sustain the effect.
Promising Results in Adult Smokers
Preliminary human trials have indicated NicVAX is safe and well-tolerated. Dorothy Hatsukami, Ph.D., director of the University of Minnesota Cancer Center’s Transdisciplinary Tobacco Use Research Center, was lead author of a 38-week study that included 68 active smokers who were randomly assigned one of three different doses of the vaccine or a placebo.
Although the study was not designed to measure the vaccine’s ability to help smokers quit, it showed that 38 percent of the participants in the group that received the highest dose of the vaccine—200 milligrams—were able to stop smoking for at least 30 days, compared with 9 percent of smokers in the placebo group. An article on the research was published in Clinical Pharmacology & Therapeutics in November of 2005.
Because of those results, Hatsukami is optimistic that the vaccine could be used as a complement to counseling or even existing drug therapies such as Zyban that are used to help smokers quit.
The prospect of a tobacco vaccine is exciting not only to physicians and patients but also to insurers. Nicotine is notoriously hard to quit. Only about 3 percent to 7 percent of smokers who try to quit on their own are still tobacco-free one year later, according to Marc Manley, M.D., vice president and medical director of population health for Blue Cross and Blue Shield of Minnesota. Even with the best treatment, which includes counseling and medications such as nicotine replacement and Zyban, only about 25 percent of smokers are still tobacco-free one year later. “There is certainly a place for the medical treatment of nicotine dependence,” he says.
On the Fast Track
The real advantage of the vaccine is that it targets the drug rather than the brain, Hatsukami says. This results in milder side effects (soreness at the injection site, headache, and malaise) than those associated with neurotransmitter drugs. Pentel says drugs that target nicotine receptors in the brain potentially can affect cognition, memory, emotion, and the body’s natural reward system.
In March, the Food and Drug Administration granted NicVAX’s manufacturer, Nabi Biopharmaceuticals of Boca Raton, Florida, a fast-track application to speed up the drug’s review process.
Nine centers across the United States, including the University of Minnesota, are recruiting smokers for a Phase 2 clinical trial to seek answers about the vaccine’s influence on quit rates and the optimal dose level and schedule for administering the vaccine. Results of that study are expected in mid 2007.
Three other companies—Cytos Biotechnology of Zurich, Switzerland, Xenova Group of Berkshire, England, and Pommune of Omaha, Nebraska—are also in the race to develop a nicotine vaccine. Xenova has also conducted human trials of a cocaine vaccine, TA-CD, where one trial found half the subjects were able to abstain from cocaine for six months.
But even if one of these companies succeeds, the nicotine vaccine won’t be a silver bullet for keeping people from becoming smokers in the first place because it only dulls the effects of smoking. The vaccine, however, does hold promise for those who are already addicted to tobacco.—Scott D. Smith