New vaccine could provide lifetime immunity to nicotine addiction

Researchers at Weill Cornell Medical College have developed a vaccine that could help existing smokers quit for good and prevent those yet to try cigarettes from ever becoming addicted. The vaccine turns the recipient’s kidney into a factory continuously churning out antibodies that clear the bloodstream of nicotine before it has a chance to reach the brain and deliver it’s addictive rush. Unlike previously tested nicotine vaccines that only last a few weeks, the effects of a single dose of this new vaccine should last a lifetime.

Generally, there are two types of vaccines. The first are active ones that activate a lifetime immune response by presenting a bit of the foreign substance, such as a piece of virus, to the immune system. Nicotine isn't suitable for active vaccines as the molecule is too small to be recognized by the immune system. The second type is a passive vaccine, which delivers ready-made antibodies to an individual. While passive nicotine vaccines have been tested, they have failed in clinical trials because they only last a few weeks and require repeated, expensive injections.

Building on previous work on a new, third kind of vaccine initially tested in mice to treat certain eye diseases and tumor types, known as a genetic vaccine, the research team at Weill Cornell took the genetic sequence of an engineered nicotine antibody and put it into an adeno-associated virus (AAV), which is a virus engineered not to 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, which neutralize the nicotine as soon as it enters the bloodstream.

The vaccine has only been tested in mice, but these mice studies showed that the vaccine produced high levels of the antibody continuously, which the researchers measured in the blood of the mice test subjects. They also discovered that little of the nicotine they administered to the experimental mice reached the brain. The activity of the mice treated with both the vaccine and nicotine remained unaltered, while the mice that weren’t treated with the vaccine basically “chilled out” after receiving nicotine. They relaxed and their blood pressure and heart activity were lowered, indicating that the nicotine had reached the brain and cardiovascular system.

Dr. Ronald G. Crystal, chairman and professor of Genetic Medicine at Weill Cornell Medical College says that, if found to have the same effects and be safe for human use, the vaccine would be best used in smokers that 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.

However, he adds that it might also be possible to use the vaccine to preempt nicotine addiction in those that 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," 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."

The researchers will next test the vaccine in rats and then primates, before ultimately testing it in humans.

The team’s work is described in the journal Science Translational Medicine.

Source: Weill Cornell Medical College