By using gene therapy to create a novel antibody that gobbles up nicotine before it reaches the brain in mice, scientists say they may have found a potential smoking vaccine against cigarette addiction. However, there is still a long way to go before the new therapy can be tested in humans.
In a study reported in the journal Science Translational Medicine this week, Researchers at Weill Cornell Medical College in New York City show how a single dose of the vaccine protected mice, over their lifetime, against nicotine addiction.
The addictive properties of the nicotine in tobacco smoke is a huge barrier to success with current smoking cessation approaches, say the authors in their paper.
Previous work using gene therapy vaccination in mice to treat certain eye disorders and tumors, gave them the idea a similar approach might work against nicotine.
The new anti-nicotine vaccine is based on an adeno-associated virus (AAV) engineered to be harmless. The virus carries two pieces of genetic information: one that causes anti-nicotine monoclonal antibodies to be created, and the other that targets its insertion into the nucleus of specific cells in the liver, the hepatocytes.
The result is the animal’s liver becomes a factory continuously producing antibodies that gobble up the nicotine as soon as it enters the bloodstream, denying it the opportunity to enter the brain.
The researchers write:
“In mice treated with this vector, blood concentrations of the anti-nicotine antibody were dose-dependent, and the antibody showed high specificity and affinity for nicotine.”
Regular blood measurements showed the vaccine was being produced at high levels continuously for at least 18 weeks.
The researchers found that the antibodies shielded the brain from nicotine they systematically gave to the mice, reducing brain nicotine levels to 15% of those of mice that had not been vaccinated.
Using infrared beams in the animal cages, the researchers measured the physical activity of mice treated with nicotine and the vaccine, and another group that received nicotine but no vaccine.
The nicotine plus vaccine group showed no change in physical activity, from before the treatment to after. The nicotine only group showed a marked change: they relaxed and their blood pressure and heart rate lowered, signs that the nicotine had reached the brain and cardiovascular system to produce the “chilled out” effect familiar to smokers.
The authors write that treatment with the vaccine, “blocked nicotine-mediated alterations in arterial blood pressure, heart rate, and locomotor activity”.
Lead investigator Dr Ronald G Crystal , chairman and professor of Genetic Medicine at Weill Cornell Medical College, told the press:
“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.”
“Our vaccine allows the body to make its own monoclonal antibodies against nicotine, and in that way, develop a workable immunity,” he added.
Other groups have developed nicotine vaccines, but they failed in clinical trials because they deliver nicotine antibodies directly. These only last a few weeks and the injections, which are expensive, have to be given again and again, said Crystal.
The other disadvantage of these previous approaches, which use a passive vaccine, is that the results are not consistent, and different people may need different doses, especially if they start smoking again, he added.
Crystal said although so far they have only tested their new vaccine in mice, they are hopeful it will help the millions of smokers who have tried to stop, but find their addiction to nicotine is so strong, none of the cessation methods currently available can overcome it.
Research shows that 70 to 80% of quitters start smoking again within 6 months, said Crystal.
The team is getting ready to test the new vaccine in rats and primates. If those trials are successful, then they can start working towards human trials.
If the vaccine successfully completes this long journey, Crystal thinks it will work best for smokers who are really keen to quit.
“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 said they would also be interested in seeing if the vaccine could be used to prevent nicotine addiction in the first place, but that is only a theory at this point, he noted.
1 in 5 adult Americans smokes. Cigarettes contain 4,000 chemicals harmful to health, leading to diseases that are responsible for 20% of deaths in the US. But it is only one of them, nicotine, that keeps smokers hooked.
Funds from the National Institutes of Health, the National Foundation for Cancer Research, and the Malcolm Hewitt Wiener Foundation helped pay for the research.
Written by Catharine Paddock