Nicotine Vaccine Promising for Smoking Cessation

Megan Brooks

An experimental nicotine vaccine reduces the amount of nicotine that reaches the brain and binds to nicotinic acetylcholine receptors (nAChRs), helping to reduce cigarette use and cravings, new research shows. However, at least 1 expert has some misgivings about its potential as an effective treatment.

“It appears that the vaccine may help with smoking cessation, but likely as an adjunct to existing pharmacology or psychological treatments,” Irina Esterlis, PhD, assistant professor of psychiatry and diagnostic radiology, Yale University, New Haven, Connecticut, told Medscape Medical News.

The nicotine vaccine is being developed by Nabi Biopharmaceuticals of Rockville, Maryland, under the brand name NicVAX. It consists of a chemical derivative of nicotine linked to a protein to induce an immune response. The nicotine-antibody complexes are too large to cross the blood-brain barrier, reducing the amount and rate of nicotine that enters the brain and, consequently, the reinforcing and addictive effects of nicotine.

The latest study with NicVAX, published online February 22 in the American Journal of Psychiatry, involved 11 smokers who smoked an average of 19 cigarettes per day, had smoked for 10 years on average, and met criteria for nicotine dependence. They received 4 injections of the nicotine vaccine (400 μg per injection, 4 weeks apart).

The participants underwent single-photon emission computed tomography (SPECT) before and after immunization. On scan days, baseline scans were followed by intravenous administration of nicotine at a dose equivalent to the nicotine delivered by 1.5 cigarettes.

Participants were asked to abstain from nicotine for 5 days before each SPECT scan; not all of them were successful.

Reduces Reward

Dr. Esterlis and colleagues report that the nicotine vaccine led to a 12.5% reduction in nicotine binding to nAChRs, which was associated with a 23.6% decrease in the amount of nicotine available to enter the brain after vaccination.

“This is important given that it may be enough to reduce some of the rewarding properties of tobacco smoking,” said Dr. Esterlis. From baseline to vaccine completion, participants reduced their cigarette use by 40% and reported a significant reduction in craving for cigarettes.

However, the American Psychiatric Association notes that a phase 3 study of the vaccine reported in 2011 yielded disappointing clinical results, showing that the vaccine was no more effective than placebo.

Dr. Esterlis and colleagues say there are several potential explanations for the discrepancy in outcomes. It is possible that the levels of antibody titers may have been suboptimal in the majority of the smokers in the clinical trial or that the 12.5% reduction in binding may not be sufficient to lead to improved abstinence rates.

They also note that the phase 3 trial compared smoking cessation outcomes for vaccination and placebo months after the vaccination schedule, whereas the present study concentrated on the period immediately after immunization.

“It appears that vaccination alone may not be the answer to smoking cessation,” said Dr. Esterlis. “It is likely that individuals still need cognitive-behavioral support or other pharmaceutical treatment (such as partial agonists at the receptor) to aid with smoking cessation.”

Not a Fan

Jacques Le Houezec, PhD, from the UK Centre for Tobacco Control Studies, University of Nottingham, England, who was not involved in the study, told Medscape Medical News that he is “not a great fan” of nicotine vaccines and “hardly believes it could get through some day.”

However, the “next generation” nicotine vaccine that has been tested in mice “could be a little better, but I’m not sure,” he said.

Regarding this latest study, Dr. Le Houezec said that for him, the “12.5% reduction in binding means nothing in terms of abstinence or even reduction; 40% reduction in cigarette use doesn’t mean 40% in nicotine intake. Smokers can get as much as they want from a cigarette. They titrate nicotine very well.”

Nonetheless, there remains considerable interest in developing vaccines for nicotine addiction and other addictions, as reported recently by Medscape Medical News.

For example, a conjugate vaccine consisting of a cocaine analog coupled to the capsid proteins of noninfectious, disrupted adenovirus has been shown to blunt cocaine highs in mice.

The study was supported by grants from the National Institute of Mental Health and the National Institute on Drug Abuse and by a grant from the Canadian Institutes of Health Research. Several of the authors have relationships with Nabi Biopharmaceuticals. A complete list of such relationships can be found with the original article. Dr. Le Houezec is a consultant for Johnson & Johnson, which makes Nicorette, and he writes a newsletter for smoking cessation specialists for Pfizer France.

Am J Psychiatry. Published online February 22, 2013. Abstract