Current status of immunologic approaches to treating tobacco dependence: Vaccines and nicotine-specific antibodies

Abstract

In contrast to current pharmacotherapies, immunologic approaches to treating tobacco dependence target the drug itself rather than the brain. This approach involves the use of nicotine-speci¿ c antibodies that bind nicotine in serum, resulting in a decrease in nicotine distribution to the brain and an increase in nicotine's elimination half-life. This review summarizes the literature examining the effects of immunologic interventions on the pharmacokinetics and behavioral effects of nicotine in animal models, as well as recent phase I and II clinical trials in humans. Studies using various vaccines and nicotine-speci¿ c antibodies in rodents have shown that immunization can signi¿ cantly reduce the behavioral effects of nicotine that are relevant to tobacco dependence (eg, nicotine self-administration). These ¿ ndings provide proof of principle that immunologic interventions could have utility in the treatment of tobacco dependence. Thus far, phase I clinical trials of nicotine vaccines have not produced any serious adverse events in humans and have produced dose-dependent increases in serum antibody levels. Although preliminary data from these small trials suggest that vaccination can facilitate abstinence from tobacco use, more advance trials are needed. By acting outside the nervous system, immunologic approaches are less likely to produce the adverse side effects associated with current medications. In addition, the unique mechanism of action of immunotherapy makes it particularly suitable for combination with other pharmacological approaches. Taken together, the work completed to date provides substantial evidence that immunologic interventions could play an important role in future treatment strategies for tobacco dependence.

Vaccines to combat smoking

“…Several individuals have speculated that antibodies that sequester this portion of nicotine early, before it reaches the CNS, will be more effective since these early effects appear to mediate reward and other psychoactive processes maintaining smoking [4][5][6]. We agree with this conjecture.…”

“…Indeed, this lag time from treatment to onset of effectiveness makes active immunization more likely to be useful for prevention of relapse rather than promoting initial cessation (7,8). Passive immunization with a monoclonal antibody has been suggested as a solution to fill this lag; that approach, however, will likely be more expensive and have increased risk of side effects such as allergic reactions [4,6]. Research advances elucidating the processes underlying the efficiency and proficiency of each vaccination to induce a drug-specific immune response, as well as improve the quality of the antibody produced (e.g., increased binding affinity, longer half-life, etc.)…”

“…from entering the CNS (e.g., [3][4][5]). A vaccinated individual will have antibodies for nicotine (see Figure 1).…”

“…Such vaccine designs have clearly demonstrated utility in inducing the anti-nicotine antibody responses necessary for alteration of nicotine-induced psychoactive effects in rodents [4,8], and the results from early initial treatment trials with several different vaccine designs show therapeutic promise [9][10][11]. Immunotherapies for smoking cessation might have some advantages over pharmacotherapies [7,12].…”

“…A comprehensive review of the research or immune system processes involving vaccines designed for treating smoking is beyond the goal and scope of a Future Perspectives article. Thus, we refer the reader to the following recent reviews [4,6,7] for excellent and detailed discussion of vaccines to combat drug addiction.…”