Researchers are getting closer to developing a vaccine that could help protect people from the addictiveness of nicotine.
The novel vaccine, which has so far been tested only in mice, prompts the body to manufacture an antibody that is attracted to nicotine. The antibodies patrol the bloodstream, soaking up the chemical and preventing it from reaching receptors in the reward centers of the brain, thereby countering the pleasure and addictiveness of smoking.
Nicotine vaccines have been tried before but failed because researchers couldn’t maintain high enough levels of antibody in smokers’ blood to block the drug’s effect. One previous attempt, called NicVax, delivered nicotine encased in a cholera toxin directly to the body in hopes that the immune system would recognize the invader and make antibodies against it. Problem is, nicotine is too small a molecule to trigger the robust immune response needed to inhibit its addictive effects.
So, rather than delivering nicotine itself, or ready-made antibodies against it, researchers led by Dr. Ronald Crystal, chairman of the department of genetic medicine at Weill Cornell Medical College, tried a different method: gene therapy. Crystal and his colleagues’ approach involved using a cold virus to ferry in the genes needed to make the nicotine antibody; the vaccine also contained instructions for infecting the liver, which is a factory for churning out proteins and other compounds. Once the vaccine infected liver cells, they began producing copy after copy of the antibody and releasing them into the bloodstream.
In the mouse experiments, the scientists found that inoculated animals were still making the antibody weeks after receiving the vaccine. They also showed that when vaccinated mice were injected with nicotine, the antibodies in their blood bound to it and prevented it from getting to the brain. Compared with mice treated with placebo, those that got the vaccine had less nicotine in their blood and just a fraction — 15% — of the chemical in their brains.
The scientists further studied the animals’ activity in their cages and found that mice treated with the experimental vaccine appeared to be immune to the effects of nicotine. In unvaccinated mice, nicotine basically chilled them out — they relaxed and their blood pressure and heart activity dropped — signs that the nicotine had reached the brain and cardiovascular system. In contrast, vaccinated mice had no response to the drug.
The scientists say enough of the antibody was measured in the animals’ blood to theoretically curb a nicotine habit. The next step would be to prove just that, says Crystal, by giving the vaccine to mice addicted to nicotine and then testing whether it affects how many times they press a lever to receive the drug.
“The idea would be for people who want to stop smoking, we would immunize them and they now have antibodies floating around in their blood on a permanent basis against nicotine,” says Crystal, whose study was published in the journal Science Translational Medicine. “So should they smoke, or smell someone else smoking, they would not get any positive reinforcing aspects of smoking because the nicotine was not reaching their brain.”
If the vaccine proves successful, it could give a leg up to people who want to quit. Currently, fewer than 30% of people who try anti-smoking drugs remain off their cigarettes for six months or more, and nicotine patches and gum don’t work much better.
Whether or not the vaccine will work in humans, however, remains to be seen. Human trials are still years away; Crystal first has to complete the additional research necessary to ensure that the strategy is safe and ready to be tested in people. Will we be “able to generate enough antibodies in humans? We need a lot of anti-nicotine Pac-Men running around in the blood to do that,” Crystal says. “And until we do the human studies, we won’t know.”