MADISON, Wis. – 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, the vaccine could become part of a new generation of smoking cessation treatments that attack dependency in the brain instead of just replacing the nicotine from cigarettes in a less harmful way, like 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.

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.

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.

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.