Researchers at Weill Cornell Medical College have developed and successfully tested an innovative vaccine that can treat nicotine addiction in mice with just one single dose.
The study, published in the journal Science Translational Medicine describes that a single dose of the novel vaccine protects mice against a life-long addiction against nicotine.
The vaccine uses the animal’s liver as a production site to continuously produce antibodies that instantly gobble up nicotine the moment it enters the bloodstream, and therefore prevents the chemical from reaching the brain and heart.
Leading researcher, Dr. Ronald G. Crystal, chairman and professor of Genetic Medicine at Weill Cornell Medical College explains:
“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.”
He continues saying: “Our vaccine allows the body to make its own monoclonal antibodies against nicotine, and in that way, develop a workable immunity.”
Dr. Crystal stated that the reason why earlier nicotine vaccines failed in clinical trials was because they all directly deliver nicotine antibodies. Their effect only lasted a few weeks and therefore required repeated, costly injections. He adds that this impractical, passive vaccine also delivered inconsistent results, which could potentially be because each person may require a different dose, particularly if the person starts to smoke again.
Crystal says:
“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 adds that evidence has shown that 70 to 80% of smokers who try to quit pick up the habit again within six months.
Around 20% of American adults smoke, and what keeps smokers addicted is the nicotine in the tobacco, and not the 4,000 chemicals in the burning cigarette that cause smoking-related health problems and which lead to one in every five deaths in the U.S.
Generally, there are two kinds of vaccines; an active and a passive vaccine. The active vaccine, for instance, those used to protect humans against polio, mumps, etc. contains a small amount of the foreign substance, like a piece of virus that enters the immune system. The immune system recognizes the foreign body and activates a lifetime immune response against the intruder. However, because nicotine is a small molecule, the immune system fails to recognize it, which prevents it from being developed into an active vaccine.
In contrast, the passive vaccine delivers readymade antibodies to prompt an immune response. For instance, delivering identically produced (monoclonal) antibodies that bind on to growth factor proteins on breast cancer cells blocks their activity.
The Weill Cornell research team designed a new, third kind of vaccine, which is a genetic vaccine. They first tested the vaccine in mice to treat certain eye diseases and tumor types before using the new nicotine vaccine on this model.
Co-author Dr. Jim D. Janda, from The Scripps Research Institute created a genetic sequence of an engineered nicotine antibody. The team then placed this antibody into an adeno-associated virus (AAV), i.e. a harmless engineered virus, and included information that directed the vaccine to go to the liver cells (hepatocytes). Once the antibody’s genetic sequence reaches the liver, it inserts itself into the hepatocytes nucleus, where the cells start to produce a steady stream of the antibodies in addition to all the other molecules they produce.
The researchers observed that the vaccine continuously produced high levels of the antibody in mice when they measured the animals’ blood, and that only a small amount of the administered nicotine in these mice reached their brain. They tested the mice’ activity that were treated with both a vaccine and nicotine, noting that it remained unchanged as the infrared beams in their cages showed that they were just as active as before the animals received the vaccine. However, mice that were given nicotine but that did not receive the vaccine just “chilled out”. The mice relaxed and their blood pressure and heart activity decreased, which are signs of the nicotine reaching the brain and cardiovascular system.
Before this novel nicotine vaccine can be tested in humans, the researchers will test it in rats and then in primates. If successful, Dr. Crystal says, this vaccine would best be used in smokers who are committed to quitting.
He continues: “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.”
The doctor says that if the vaccine proves completely safe, it may be possible to prevent individuals who never smoked from getting addicted to nicotine, in the same way as vaccinations are given to prevent various disease-producing infections. He remarks: “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. We would of course have to weight benefit versus risk, and it would take years of studies to establish such a threshold.”
Dr. Crystal concludes: “Smoking affects a huge number of people worldwide, and there are many people who would like to quit, but need effective help. This novel vaccine may offer a much-needed solution.”
Written by Petra Rattue