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Vaccine May Block the Effect of Nicotine

June 27, 2012 -- Scientists say they've developed a vaccine that may one day protect people against the addictive effects of nicotine -- but for now they have to settle for some success in mice.

The vaccine uses the shell of a harmless virus that, much like the Trojan horse, carries into cells genetic instructions for making an antibody against nicotine. When cells are "infected" by the virus, they get tricked into churning out a protein that blocks nicotine's biological effects.

"It's sort of like having Pac-Man floating around in the blood. [The antibodies] bind to the nicotine and prevent it from reaching its receptors in the brain," says Ronald G. Crystal, MD, chairman and professor of genetic medicine at Weill Cornell Medical College in New York City.

Researchers have tried to vaccinate people against nicotine before -- by directly injecting antibodies into the blood. The problem is that the antibodies disappear after only a few weeks, and the studies ultimately had disappointing results.

This time, researchers say they may have found a way to get the body to keep making more.

Testing a Vaccine Against Nicotine

In a study published in the journal Science Translational Medicine, Crystal and colleagues at Scripps Research Institute in La Jolla, Calif., described how they were able to successfully vaccinate mice against nicotine.

First, they injected mice with a viral shell that contained instructions for making the nicotine antibody. The viral shell also contained instructions to harmlessly infect the liver cells of the mice with these instructions, thus essentially using the liver as a factory to continuously churn out antibodies that attach to nicotine once it hits the bloodstream.

Weeks later, they found antibodies against nicotine in the blood of the treated mice.

Next they were able to show that if they injected the mice with nicotine -- about the amount in two cigarettes -- the antibodies in their blood would bind to the nicotine and prevent it from getting to the brain.

The mice treated with the experimental vaccine had more nicotine in their blood than mice treated with a placebo vaccine, and nearly all of it (83%) had been captured by an antibody. The mice injected with the active vaccine also had far less nicotine in their brains compared to the placebo-treated mice.

Finally, researchers showed that vaccinated mice didn't appear to experience any of the physical effects of nicotine.

"If you give a mouse nicotine, they do what humans do, they sort of chill out," Crystal says. "They run around a lot less, their blood pressure and heart rate drop a little bit. If we give nicotine to a mouse that's been immunized by this genetic vaccine, it's like giving the mouse water. They don't respond at all," he tells WebMD.

Michael Fingerhood, MD, medical director of the comprehensive care practice at Johns Hopkins Bayview Medical Center in Baltimore, Md., who specializes in the treatment of addiction, called the vaccine a promising approach that warranted more research.

But he noted that there are already medications, such as Chantix, that work by blocking nicotine's effects. Not everyone who uses them is able to successfully quit smoking.

He says that suggests that the addiction to cigarettes goes deeper than the biological effects of nicotine.

"I think smoking is perhaps the most complicated of addictions because there are other aspects to why people have trouble quitting smoking," says Fingerhood, who reviewed the study for WebMD but was not involved in the research.

"Is it a good technique, absolutely, but I don't think it's going to be a panacea," he says. "It may be another way to help our patients."

Crystal agrees. "The caveat of the study is that humans are not just big mice. It works great in mice, but we'll have to see and eventually do a human study."

One thing he wonders about, for example, is whether people could out-smoke the vaccine.

"Could they overpower the vaccine by smoking many cigarettes? We don't know the answer to that," he says.

In research, there are many steps between testing something in mice and testing it in people. Human trials are likely to be years away.

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