Doctors are testing a radical new way to help smokers quit: a shot that "immunizes" them against the nicotine rush that fuels their addiction.

That pleasurable buzz has seduced Mario Musachia into burning through nearly half a million cigarettes in half a century.

Now the Madison man is among 300 people around the country who are testing an experimental vaccine that makes the immune system attack nicotine in much the same way it would fight a life-threatening germ.

The treatment keeps nicotine from reaching the brain, making smoking less pleasurable and theoretically, easier to give up. The small amount that still manages to get in helps to ease withdrawal, the main reason most quitters relapse.

If it works — and this has not yet been proved -- the vaccine could become part of a new generation of smoking cessation treatments. They attack dependency in the brain instead of just replacing the nicotine from cigarettes in a less harmful way, like the gum, lozenges, patches and nasal sprays sold today.

One such drug, Pfizer Inc.'s Chantix, is due on the market any day now. Another, Sanofi-Aventis SA's Acomplia, recently won approval in Europe as a weight-loss drug. If U.S. regulators follow suit, some doctors say they also will use it to help smokers quit, especially those concerned about gaining weight.

"The typical patient is a 30-year-old woman who says, 'If I gain 5 pounds, I'm going back,'" said Dr. J. Taylor Hays, a smoking cessation expert at the Mayo Clinic in Rochester, Minn., who helped test Chantix and other treatments.

Other novel drugs are in development, but NicVax, by Nabi Biopharmaceuticals, a Boca Raton, Fla., biotech company with labs in Rockville, Md., is most advanced among the vaccines.

After four smaller studies suggested it might be safe and effective, the new, larger study was started in Madison, Minneapolis, Omaha, San Francisco, Los Angeles, Boston and New York City. (People interested in participating must contact the company, but few volunteer openings are left.)

The Food and Drug Administration has granted the vaccine fast-track status, meaning it will get prompt review, and the National Institute on Drug Abuse just gave Nabi a second $4 million grant to finance the study and NicVax's development.

"It's going to be a very good way to keep people from relapsing," predicts Dr. Frank Vocci, director of medications development at the federal institute.

Relapse is the biggest problem quitters face.

Of the more than 48 million smokers in the United States, 40 percent each year make a serious attempt to quit, but fewer than 5 percent succeed long-term. Nicotine replacement products combined with counseling can double that rate, but most quitters don't try them. Two-thirds go back to smoking within a month.

"When they have that first cigarette, if they really enjoy it, they're at high risk of relapse. If you can make that cigarette not so good, you've really got something," Vocci said.

The possibility that a simple shot could do this is what lured Musachia to the Center for Tobacco Research and Intervention on the fringes of the University of Wisconsin-Madison campus earlier this month. He has tried many ways to quit but still smokes.

"I'm sick of it. I'm surprised I've lived this long," said the 75-year-old man. "My kids — they carry on like 2-year-olds when I smoke around them. My animals run and hide."

He and other participants will get four or five shots, either four or six weeks apart, and will be studied for a year. Two-thirds will get the vaccine; the others, dummy shots. Neither they nor the doctors will know who got what until the study ends.

They also will get counseling and must set a quit date, usually around the second shot, because the first shot is just meant to "prime" the immune system. Subsequent doses make it produce antibodies, which latch onto nicotine in the bloodstream and keep it from crossing the blood-brain barrier and getting into the brain where it maintains the addiction.

"They won't get the rush, the reward," but the small amount still getting in "we think is an advantage," because it should lessen withdrawal symptoms, said Dr. Henrik Rasmussen, Nabi's chief medical officer.

The antibodies should remain in the system for up to a year; booster shots may be needed after that, but this needs more study, Rasmussen said.

The new drugs come at a time of heightened attention to helping smokers quit. Last month, the National Institutes of Health held a conference to review the scientific evidence for what smoking cessation techniques work.

Earlier this month, two large scientific conferences were held in Washington, D.C., on the topic.

Research money has increased because of tobacco lawsuit settlements, and insurers increasingly see the health burden of smoking and will pay for cessation treatments that work, said Douglas Jorenby, the psychologist who heads the NicVax study in Madison.

Smokers also are demanding better results than those afforded by traditional nicotine replacement tools. Their desperation sometimes makes them prey to quacks.

The FDA recently moved to block some companies promoting low-power laser therapy, or laser acupuncture, as a way to quit, and a consumer's group is seeking action against a bottled water product that contains nicotine.

"We've got 20 million Americans trying to quit. Among those trying, less than 20 percent are using evidence-based treatments," said Dr. Michael Fiore, director of the tobacco research center in Madison.

The vast majority of these visit a doctor for routine care, yet "few of them, less than a third, leave that encounter with evidence-based advice on how to quit smoking," he lamented.

Regardless of whether the experimental vaccine or other novel approaches ultimately prove successful, they already have had a positive effect — giving some smokers fresh motivation, Jorenby said.

"Every time there's a new treatment for smoking cessation, there are people who have never tried to quit, or haven't tried for a long time, who are going to give it a shot," he said. "People benefit from practice. It usually takes several tries."