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 – 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.

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.