Tobacco: a genetic vaccine against nicotine to quit smoking?

This could be great news for all smokers who want to quit. Researchers from Weill Cornell Medical College (New York) announce that they have developed a potential vaccine capable of blocking the effects of nicotine, which can be used for people addicted to tobacco.

Intent is nothing new. Several vaccination techniques have already been proposed but they have all proved unsuccessful. The first, considered passive, required the intravenous injection of antibodies directed against nicotine. Added to the disadvantage of the limited efficacy over time was the high cost and the problems of adjusting the doses according to the patients and their smoking history. Active vaccination, which consists of directly stimulating the immune system, is more difficult to implement, due to the too small size of nicotine. However, a test is currently underway on a product using nanoparticles.

A genetic vaccine that stimulates the synthesis of antibodies

This time, researchers propose in Science Translational Medicine a genetic vaccine. An adeno-associated virus (adenovirus), carrying the DNA sequence making it possible to synthesize an antibody against nicotine, was injected once into mice. This viral vector, harmless to animals and humans, inserts its genome into that of rodent liver cells, transforming the liver into an antibody production factory.

From mice to humans: will the nicotine vaccine produce the same effect when tested on humans? We will have to be patient to know the answer, which will come in a few years. © Pascal Dolémieux, Sanofi Pasteur, Flickr, cc by nc nd 2.0

To verify the effectiveness of the technique, a high dose of nicotine (equivalent to the content of two cigarettes) was injected into the mice. In the brains of vaccinated animals, the nicotine concentration fell by 85%. The physical effects of the molecule were measured. If the rodents of the control group showed signs of relaxation, with a drop in blood pressure and heart rate as well as some locomotor changes, none of these symptoms were observed in the treated mice.

Anti-nicotinic antibodies successfully sequester the molecule they target, since 83% of the nicotine found in the blood was bound to its immunoglobulin G (the antibody protein), ie seven times more than in control animals. The immune complexes thus formed are then metabolized and excreted in the urine.

Eighteen weeks after the injection of the vaccine, the antibody levels remained as high as ever. The authors assume that this could extend over the life of the animal and hope that such an effect could be observed in humans.

Immunize teenagers to nicotine

Because in the long term, as we can guess, their ambition is not to save mice from a nicotine overdose, but to develop a vaccine for help those who wish to quit smoking. The team is not at its first attempt since, at the beginning of 2011, it published in Molecular Therapy the same process for a vaccine against cocaine.

The earlier you start smoking, the greater the risk of tobacco addiction. Should adolescents be vaccinated against nicotine to prevent them from becoming addicted? © Nationaal Archief, Wikipedia, DP

Nicotine, one of the 4,000 substances found in a cigarette, has been blamed for tobacco addiction, giving pleasure to the person who ingests it by modifying brain activity. The researchers believe that by preventing the molecule from acting, the patient will no longer feel the pleasure associated with cigarettes, which will help him to quit permanently.

The principle is simple, but does it really work? First of all, it is not known whether the same effect will be found in humans. Clinical trials will be launched only when the protocols have been applied to rats and non-human primates. Finally, even if 15% of the nicotine in a cigarette ends up in the brain, we cannot yet predict whether this will be enough to quit smoking.

On the other hand, such a vaccine does not rid the craving for nicotine, it simply makes the craving impossible to fill. This deprivation risks causing psychological disorders such as depression, at least temporarily, and suggests that complementary therapies should be put in place to accompany the patient until definitive withdrawal. In the end, we should not expect miracles from this vaccine and hope that it will become the ultimate solution for quitting smoking without suffering.

Another point, raised by Ronald Crystal, the researcher who supervised the work, is causing controversy. He suggests that this preventive treatment could be injected into adolescents before they have even touched a cigarette. "In the same way that parents decide to vaccinate their child against the papillomavirus, they could decide to protect him also from nicotine," he said in a press release. Is avoiding addiction at the source the best solution?