Nicotine Conjugate Vaccine as a Novel Approach to Smoking Cessation

Anne R. Ottney, Pharm.D

Disclosures

Pharmacotherapy. 2011;31(7):703-713. 

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Place in Therapy

The true clinical utility of the 3′-AmNic-rEPA vaccine is yet to be identified. Although no head-to-head comparison trials have been completed, patients receiving the nicotine vaccine have exhibited comparable quit rates at 6 months to approved first-line smoking cessation drugs.[8] A combination of behavioral therapy with the 3′-AmNic-rEPA vaccine is being evaluated in phase III trials. Research results support higher quit rates with all smoking cessation drugs when combined with counseling than either intervention alone.[8]

Smokers' interest in using a vaccine as a method to quit was assessed by an online survey.[26] Approximately 55% of smokers surveyed indicated that they would be likely to very likely to access a nicotine vaccine in an effort to quit smoking should one become available. Those smokers who had made five or more previous quit attempts and those who had tried multiple methods to quit in the past were more likely to view the vaccine as a future option for cessation. The 3′-AmNic-rEPA vaccine represents a potential advantage to currently available nicotine addiction treatments, with the benefit of requiring only once-monthly dosing compared with daily administration, thereby enhancing adherence.

Specific populations, such as those with psychiatric disorders, cardiac or respiratory disease, recent history of alcohol or drug abuse, and individuals older than 65 years have largely been excluded from clinical trials involving the 3′-AmNic-rEPA vaccine. These groups are representative of high-risk populations who stand to gain significant benefit from quitting smoking. Clinical trial data indicate that the 3′-AmNic-rEPA vaccine causes very few systemic adverse effects due to minimal central nervous system absorption and high specificity for the nicotine molecule. No evidence of adverse effects that would be more harmful to these populations has been found (e.g., precipitation of suicidal ideations, increased heart rate). Data do not show a significant difference in the ability of vaccinated subjects to generate nicotine-specific antibodies with increasing age. Further trials to explore the efficacy of the nicotine vaccine in specific, high-risk populations are needed.

Combination of the 3′-AmNic-rEPA vaccine with other smoking cessation therapies is possible. As 3′-AmNic-rEPA binds any nicotine particles introduced into the bloodstream, combination with nicotine replacement therapy products, such as the patch, gum, lozenge, inhaler, or nasal spray, in theory, would not provide additional benefit in the cessation attempt, as the vaccine would sequester the nicotine molecules in the periphery. Concern that nicotine from nicotine replacement products may compete for antibody binding sites has largely excluded the use of these products from clinical trials with the 3′-AmNic-rEPA vaccine. The vaccine combined with bupropion would be a feasible option, as each has a distinct mechanism of action in smoking cessation. Bupropion inhibits reuptake of dopamine in the central nervous system, increasing dopamine levels through a similar reward pathway as smoking, whereas the nicotine vaccine has no effect on neurotransmitter release. An ongoing European study is being conducted to determine if combining the 3′-AmNic-rEPA vaccine with varenicline is more effective than varenicline plus a placebo injection.[27] As 3′-AmNic-rEPA does not completely eliminate nicotine distribution to the brain, adding varenicline may provide the patient with additional protection from the rewarding and reinforcing properties of cigarettes.

As 80% of smokers begin smoking by age 18 years, the potential exists for the 3′-AmNic-rEPA vaccine to be a prophylactic method to inhibit tobacco smoking initiation in children and adolescents.[28] In human studies, the 3′-AmNic-rEPA vaccine has been used solely as a means to treat tobacco dependence, not to prevent initiation of tobacco use. Studies to evaluate the usefulness of a prophylactic method of vaccination are ongoing. To our knowledge, the 3′-AmNicrEPA vaccine has not been tested in individuals using chew tobacco or other forms of smokeless tobacco.

The standard of care for smoking cessation in pregnant women is cognitive behavioral therapy, although the potential for the 3′-AmNic-rEPA vaccine to be used in this population exists. A study performed with human placentas revealed the administration of rabbit Nic-IgG, an immunoglobulin with high affinity for nicotine produced in response to 3′-AmNic-rEPA, reduced the transfer of nicotine into the fetal circuit by approximately 93% with negligible absorption into the placenta.[29] An advantage of the 3′-AmNic-rEPA vaccine in pregnancy in addition to behavioral therapy may be reduced fetal exposure to nicotine if the woman is not able to quit smoking during her pregnancy or experiences a relapse. Unfortunately, the vaccine provides no protection to the fetus from the other harmful chemicals found in cigarettes.

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