The DNA injection, just a shot of which makes antibodies against nicotine, could also be used to vaccinate children to stop them ever getting hooked, researchers said.
The jab has so far been tested on mice, but researchers hoped that human trials could begin in as little as two years, the Daily Mail reported.
The jab contains genes "programmed" to make antibodies that neutralise nicotine before it reaches the brain, where it would normally trigger the pleasurable feelings that underlie addiction, the researchers said.
Dr Ronald Crystal, who led the research at Weill Cornell Medical College in New York, said the theory is that if smokers no longer get such gratification from cigarettes, they will find it easier to quit.
Most smokers who try to quit light up again within six months, but "this novel vaccine may offer a much-needed solution," he said.
The injection tricks the liver into continuously making antibodies, ensuring there are always some in the blood to fight nicotine, Dr Crystal explained.
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In the study, when vaccinated mice were given nicotine, the antibodies cut the amount that made its way to the brain by 85 per cent, with no effect on their behaviour, blood pressure or heart rate, he added.
The research, published in journal Science Translational Medicine, is still at an early stage and the need for large-scale studies means the jab is at least five years from the market.
If it is proved to be safe and effective, it could eventually be included in school vaccination programmes to stop youngsters from ever starting to smoke, Dr Crystal added.
Darren Griffin, at Kent University, said the study had "great potential", but warned that what worked in mice did not always work in man.