Researchers develop novel anti-body vaccine that blocks addictive nicotine chemicals from reaching the brain

Researchers at Weill Cornell Medical College have developed and successfully tested in mice an innovative vaccine to treat nicotine addiction.

In the journal Science Translational Medicine, the scientists describe how a single dose of their novel protects mice, over their lifetime, against . The vaccine is designed to use the animal's liver as a factory to continuously produce antibodies that gobble up the moment it enters the , preventing the chemical from reaching the brain and even the heart.

"As far as we can see, the best way to treat chronic nicotine addiction from smoking is to have these Pacman-like antibodies on patrol, clearing the blood as needed before nicotine can have any ," says the study's lead investigator, Dr. Ronald G. Crystal, chairman and professor of at Weill Cornell Medical College.

"Our vaccine allows the body to make its own against nicotine, and in that way, develop a workable immunity," Dr. Crystal says.

Previously tested nicotine vaccines have failed in clinical trials because they all directly deliver nicotine antibodies, which only last a few weeks and require repeated, expensive injections, Dr. Crystal says. Plus, this kind of impractical, passive vaccine has had inconsistent results, perhaps because the dose needed may be different for each person, especially if they start smoking again, he adds.

"While we have only tested mice to date, we are very hopeful that this kind of vaccine strategy can finally help the millions of smokers who have tried to stop, exhausting all the methods on the market today, but find their nicotine addiction to be strong enough to overcome these current approaches," he says. Studies show that between 70 and 80 percent of smokers who try to quit light up again within six months, Dr. Crystal adds.

About 20 percent of adult Americans smoke, and while it is the 4,000 chemicals within the burning cigarette that causes the health problems associated with smoking -- diseases that lead to one out of every five deaths in the U.S. -- it is the nicotine within the tobacco that keeps the smoker hooked.

A New Kind of Vaccine

There are, in general, two kinds of vaccines. One is an active vaccine, like those used to protect humans against polio, the mumps, and so on. This kind of vaccine presents a bit of the foreign substance (a piece of virus, for example) to the immune system, which "sees" it and activates a lifetime immune response against the intruder. Since nicotine is a small molecule, it is not recognized by the immune system and cannot be built into an active vaccine.

The second type of vaccine is a passive vaccine, which delivers readymade antibodies to elicit an immune response. For example, the delivery of monoclonal (identically produced) antibodies that bind on to growth factor proteins on breast cancer cells shut down their activity.

The Weill Cornell research team developed a new, third kind -- a genetic vaccine -- that they initially tested in mice to treat certain eye diseases and tumor types. The team's new nicotine vaccine is based on this model.

The researchers took the genetic sequence of an engineered nicotine antibody, created by co-author Dr. Jim D. Janda, of The Scripps Research Institute, and put it into an adeno-associated virus (AAV), a virus engineered to not be harmful. They also included information that directed the vaccine to go to hepatocytes, which are liver cells. The antibody's genetic sequence then inserts itself into the nucleus of hepatocytes, and these cells start to churn out a steady stream of the antibodies, along with all the other molecules they make.

In mice studies, the vaccine produced high levels of the antibody continuously, which the researchers measured in the blood. They also discovered that little of the nicotine they administered to these mice reached the brain. Researchers tested activity of the experimental mice, treated with both a vaccine and nicotine, and saw that it was not altered; infrared beams in the animals' cages showed they were just as active as before the vaccine was delivered. In contrast, mice that received nicotine and not treated with the vaccine basically "chilled out" -- they relaxed and their blood pressure and heart activity were lowered -- signs that the nicotine had reached the brain and cardiovascular system.

The researchers are preparing to test the novel nicotine vaccine in rats and then in primates -- steps needed before it can be tested ultimately in humans.

Dr. Crystal says that, if successful, such a vaccine would best be used in who are committed to quitting. "They will know if they start smoking again, they will receive no pleasure from it due to the nicotine vaccine, and that can help them kick the habit," he says.

He adds that it might be possible, given the complete safety of the vaccine, to use it to preempt nicotine addiction in individuals who have never smoked, in the same way that vaccines are used now to prevent a number of disease-producing infections. "Just as parents decide to give their children an HPV vaccine, they might decide to use a . But that is only theoretically an option at this point," Dr. Crystal says. "We would of course have to weight benefit versus risk, and it would take years of studies to establish such a threshold."

"Smoking affects a huge number of people worldwide, and there are many people who would like to quit, but need effective help," he says. "This novel vaccine may offer a much-needed solution."

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extremity
1 / 5 (1) Jun 27, 2012
Really neat article. Except for this:

"About 20 percent of adult Americans smoke, and while it is the 4,000 chemicals within the burning cigarette that causes the health problems associated with smoking -- diseases that lead to one out of every five deaths in the U.S."

This data correlation makes it seem that smoking will be cause of death of a smoker, and if it doesn't kill them, it will kill someone else indirectly...
be4r
not rated yet Jun 27, 2012
Not to mention the fact that the "4000 chemicals" really isn't the main cause of problems from smoking, its the fact that burning anything creates free radicals that react with DNA. It is then a select few chemicals that may promote emphysema, mainly just simple charcoal tar. "Chemicals" is such a scare tactic word in the media, and I would have hoped that a science blog would not stoop to using it as well. Everything is chemicals.
mjesfahani
not rated yet Jun 28, 2012
Addiction can only be solved by human himself, that's all.
antonima
not rated yet Jun 29, 2012
Nicotine in itself isn't addictive. Its only addictive when combined with other chemicals called MAOIs. One of these substances is naturally present in tobacco, making tobacco smoke addictive.

Haha, I can see it already, throngs of young, upright liberal parents rushing their kids to get nicotine vaccines!!
oliverrp
not rated yet Jun 29, 2012
"Haha, I can see it already, throngs of young, upright liberal parents rushing their kids to get nicotine vaccines!!"

Not one of those, but you can bet your sweet one that this old, downright questionable, conservative would rush to get the shot if it would end my 55 year addiction to nicotine. Mjesfahani is right, only the human can cure his addictions. I would add - "by any means possible!"
antonima
not rated yet Jun 29, 2012
"Not one of those, but you can bet your sweet one that this old, downright questionable, conservative would rush to get the shot if it would end my 55 year addiction to nicotine."

Is tobacco addiction really up there with measels, polio, and hepatitis, that kids may have to get vaccines as a preventative measure?
BTW I recommend trying e-cigs, they don't have the MAOIs and so are not addictive but do satisfy the craving. I smoked one for 6 months, one day it broke and I was suddenly cut-off. NO withdrawal symptoms whatsoever although they don't taste as delicious.
alfie_null
not rated yet Jun 29, 2012
Potential technique for treating addictions to other drugs?