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 vaccine protects mice, over their lifetime, against nicotine addiction. The vaccine is designed to use the animal's liver as a factory to continuously produce antibodies that gobble up nicotine the moment it enters the bloodstream, 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 biological effect," says the study's lead investigator, Dr. Ronald G. Crystal, chairman and professor of Genetic Medicine at Weill Cornell Medical College.
"Our vaccine allows the body to make its own monoclonal antibodies 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 smokers 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 nicotine vaccine. 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."
Journal reference: Science Translational Medicine
Provided by New York- Presbyterian Hospital
- Nicotine vaccine prevents nicotine from reaching the brain May 02, 2012 | not rated yet | 0
- Vaccine being developed to help smokers quit Nov 20, 2009 | not rated yet | 0
- Researchers testing vaccine to help people quit smoking May 21, 2010 | not rated yet | 0
- A vaccine for nicotine? Oct 04, 2011 | not rated yet | 0
- Vaccine blocks cocaine high in mice Jan 04, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013 Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
By discovering the new mechanism by which estrogen suppresses lipid synthesis in the liver, UC Irvine endocrinologists have revealed a potential new approach toward treating certain liver diseases.
Medical research May 23, 2013 | not rated yet | 0 |
Aortic arch pulse wave velocity, a measure of arterial stiffness, is a strong independent predictor of disease of the vessels that supply blood to the brain, according to a new study published in the June issue the journal ...
Medical research May 23, 2013 | not rated yet | 0
Since the discovery of Prontosil in 1932, sulfonamide antibiotics have been used to combat a wide spectrum of bacterial infections, from acne to chlamydia and pneumonia. However, their side effects can include serious neurological ...
Medical research May 23, 2013 | not rated yet | 0 |
Scientists at the National Institutes of Health report they have discovered in mouse studies that a small molecule released in the spinal cord triggers a process that is later experienced in the brain as ...
Medical research May 23, 2013 | 5 / 5 (3) | 0 |
Spanish researchers have discovered that the daily clearance of neutrophils from the body stimulates the release of hematopoietic stem cells from the bone marrow into the bloodstream, according to a report published today ...
Medical research May 23, 2013 | 5 / 5 (2) | 0
Two mutations central to the development of infantile myofibromatosis (IM)—a disorder characterized by multiple tumors involving the skin, bone, and soft tissue—may provide new therapeutic targets, according to researchers ...
5 hours ago | 5 / 5 (1) | 0 |
(Medical Xpress)—A new study by researchers in the US has shown that an ancient virus can be modified to help in the fight against the simian immunodeficiency virus SIV, which is the equivalent in monkeys ...
10 hours ago | 5 / 5 (3) | 0 |
Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.
7 hours ago | 5 / 5 (1) | 0 |
Biological processes are generally based on events at the molecular and cellular level. To understand what happens in the course of infections, diseases or normal bodily functions, scientists would need to ...
8 hours ago | 5 / 5 (2) | 0 |
Talking on a hands-free device while behind the wheel can lead to a sharp increase in errors that could imperil other drivers on the road, according to new research from the University of Alberta.
4 hours ago | not rated yet | 0
Kate O'Reilly's spring allergy survival kit includes the usual stuff - nasal sprays, allergy pills and a box of tissues. This season, she's added a new weapon to her line of defense: an app on her smartphone.
5 hours ago | not rated yet | 0