Researchers at Weill Cornell Medical College have successfully tested a new vaccine to treat nicotine addiction in mice.
In the journal Science Translational Medicine, the scientists describe how a single dose of the new vaccine protects mice against nicotine addiction for the rest of their lives.
The vaccine is designed to use the animal’s liver as a “factory” to continuously produce antibodies that attack nicotine the moment it enters the bloodstream, preventing it 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,” said 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.”
Previously tested nicotine vaccines have failed in clinical trials because they directly deliver nicotine antibodies, which only last a few weeks and require repeated — and expensive — injections, Crystal notes.
Passive vaccines also had inconsistent results, perhaps because the dose needed may be different for each person, especially if they start smoking again, he said.
“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 said.
The researchers used a new kind of vaccine for the study known as a genetic vaccine, which was initially tested in mice to treat certain eye diseases and tumors. They took the genetic sequence of an engineered nicotine antibody and put it into an adeno-associated virus (AAV), which was 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 manufacture a steady stream of the antibodies, along with all the other molecules they make.
In studies with mice, 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.
The researchers are preparing to test the nicotine vaccine in rats and then in primates, necessary steps before it can be tested in humans.
If successfully developed, the vaccine would work best in smokers who are committed to smoking, Crystal says. “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 said.
He added that it might be possible to use it to preempt nicotine addiction in individuals who have never smoked, in the same way that vaccines are now used 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,” he said. “We would, of course, have to weight benefit versus risk, and it would take years of studies to establish such a threshold.”
The study was funded by the National Institutes of Health, the National Foundation for Cancer Research, and the Malcolm Hewitt Wiener Foundation.
Source: Weill Cornell Medical College