To help smokers to stop smoking, there are quit smoking products but they are not always effective, particularly in the long term. Hence the need for new therapies. The vaccine against nicotine is one of the avenues of research. What is its principle? Where are the tests? Zoom on the vaccine against nicotine addiction.
Vaccine against nicotine: the principle
In cigarettes, nicotine is the addictive component. It is a natural drug also produced by the brain. And like all substances that cause addiction, nicotine increases the amount of dopamine – * which is a neurotransmitter involved in the sensation of pleasure – in the brain. The mode of action of nicotine? It mimics a natural neurotransmitter, acetylcholine, and binds to its receptors (nicotinic receptors). These receptors are carried by neurons in the reward pathway, dopamine neurons. Nicotine stimulates the neurons. More nicotinic receptors are stimulated, more dopamine is released.
* Note that our Brain cells communicate with each other through neurotransmitters.
The principle of a vaccine against nicotine addiction is as follows: neutralize nicotine in the bloodstream before it reaches the brain. For this, we must make visible the nicotine so that it is recognized by the immune system. In fact, nicotine is a very small molecule that easily passes the natural barriers to reach the brain. Hence the idea to associate nicotine inactive fraction of virus to elicit an immune response, the anti-nicotine production. In the immunized person, nicotine binds to the antibody. This complex is too large to cross the brain barrier. The amount of nicotine entering the brain is so much lower, resulting in a loss of pleasure when the person smokes.
Please note: the urge to smoke is not affected with this vaccine but smoking no longer meets this need. This vaccine could help smokers quit smoking and also to prevent relapse after stopping.
Vaccine against nicotine: several laboratories vying
Researchers around the world have been working for more than 10 years on an anti-smoking vaccine. Three laboratories are the most advanced in this research: Celtic Pharmaceuticals Holdings (vaccine Ta-Nic), GSK-Nabi (NicVAX vaccine) Cytos Biotechnology (Nic 002 vaccine). The tested vaccines are therapeutic vaccines for smokers who failed to quit smoking with other methods of weaning.
Pre-clinical studies and testing phases I and II in humans have shown that these vaccines resulted in production of anti-nicotine antibodies were well tolerated and more nicotine antibody rates were high, the more likely withdrawal were great.
In 2007, Celtic Pharmaceuticals Holdings LP has started Phase II clinical study for its anti-nicotine vaccine Ta-Nic, to ensure abstinence rates at 6 months and thus its safety. The results are not yet known, but Phase I has already shown an abstinence rate at 12 months for smokers who received the vaccine.
Earlier, phase II clinical study of NIC002 (also known as Nicotine QB or CYT002-NicQb) of Cytos Biotechnology lab has shown that the vaccine promoted and strengthened weaning smokers who stopped and antibody reached a high anti-nicotine level. However, side effects (same symptoms as the flu) appeared in many people after vaccination. In 2007, CYTOS concluded a partnership agreement with Novartis. They started in 2008 Phase II trial of the vaccine with a new formula to limit side effects. However, the first data showed that the first goal (a total withdrawal between 8 and 12 weeks after the start of treatment) was not reached. Probably because NCI002 failed to create enough antibodies.
Nabi / GSK announced successful results of Phase II for their NicVAX vaccine. It is safe and well tolerated, and it generally produces antibodies to nicotine at very high rates. In subjects vaccinated with NicVAX, a link was noted between antibody levels and their ability to quit smoking. A significant number of subjects was able to quit smoking and remain abstinent for a long time. NicVAX is currently in Phase III of its clinical trials. The laboratory aims to determine the effectiveness for smokers. If these trials are successful, the vaccine could soon be on the U.S. market.
A fellow at the independent laboratory Pharmaceutica AB is currently developing Niccine a supposed preventive treatment and a nicotine addiction vaccine. In 2008, the lab announced that the recruitment of 355 smokers for phase II clinical study was completed. The purpose of this study? To demonstrate the ability of the vaccine to prevent relapse when stopping smoking.
Vaccine against nicotine: further questions
The results are encouraging, but there are still a number of questions about the anti-smoking vaccines. Firstly the necessary reminders. With these vaccines, it is possible to protect against relapse in re-vaccination within a certain range, but for now, no study has been conducted on these boosters. In addition, intramuscular injections are painful, especially if you must do it a regular basis. Other forms of vaccine are considered. A test on mice showed that with intranasal vaccination, a significant anti-nicotine rate is obtained.
Another question about this vaccine: one might consider prophylactic vaccination would prevent becoming addicted to tobacco? This raises many questions: Can we vaccinate against a behavior and not against a disease? What about consent? For example, could parents vaccinate their children or teenagers defensively without their permission? Does this vaccination replace information on smoking and its dangers?
Finally, nicotine can be used in treatment, particularly in the context of ulcerative colitis (inflammation of the intestine). A preventive vaccine would prevent the use of nicotine as a medicament.
The vaccine against nicotine today seems an option in the fight against tobacco addiction. But it surely will not be the only answer. Research on new pharmacological approaches are also underway. And in any case, it is necessary to also add a counseling treatment.