Nicotine addiction presents a well-recognized public health challenge and, in tobacco users, likely reflects a complex interplay of neurobehavioral, genetic, environmental, and social factors (Benowitz, 2010). This consideration makes it unlikely that any single medication or behavioral intervention can serve as a panacea to effectively reduce smoking behavior across the general population. It also highlights the need to optimize multiple treatment strategies that can be flexibly used, either alone or in combination, to blunt addiction-related effects of nicotine exposure.

Immunotherapeutic strategies (eg, nicotine vaccines) have been forwarded as an intriguing alternative or adjunct treatment approach to the use of pharmacological agents for smoking cessation (Pentel and LeSage, 2014). However, despite encouraging results early in development, the several conjugated nicotine vaccines that have been tested thus far have been relatively ineffective in clinical trials—modest increases in quit rates in smokers with relatively high levels of nicotine antibodies, and no effect in smokers with low antibody levels (Hatsukami et al, 2011). Although the reasons for such outcomes are undoubtedly complex, the limited positive results suggest that, to be successful, the immunogen must induce a sufficiently strong and reliably uniform nicotine-specific response.

Recent advances in vaccine development have led to innovative nano-vaccines that produce a more consistent immune response (and, presumably, improved efficacy), with reduced side effect liability. For example, the novel synthetic nano-vaccine SEL-068 has been reported to dose-dependently induce high affinity anti-nicotine antibody titers in both mice and non-human primates (Fraser et al, 2014). To further evaluate SEL-068, we conducted behavioral studies to determine how nicotine’s discriminative-stimulus effects, which have been related to its subjective effects in humans (Smith and Stolerman, 2009), are modified by SEL-068 treatment in nicotine-naive and nicotine-trained monkeys. Results show that in the absence of other, non-specific behavioral effects, SEL-068: (a) effectively prevented the expression of nicotine’s discriminable effects in nicotine-naïve monkeys and (b) produced a long-term (>25 weeks after vaccination) and substantive reduction (6-fold) in the potency with which nicotine produced discriminable effects in nicotine-trained monkeys (Desai and Bergman, 2015). These are compelling results and provide the first evidence in a primate species that nicotine-targeting nano-vaccines can significantly reduce stimulus effects of nicotine that likely contribute to smoking behavior.

A key finding in our experiments was that SEL-068 was more effective against nicotine’s discriminable effects in naïve than nicotine-experienced monkeys. These findings suggest that the degree of immunogenicity that is necessary for successful clinical outcomes may differ according to the subject’s history of nicotine exposure. At present, it appears that nicotine nano-vaccines may be most useful as a preventative measure in non-exposed individuals—an ethically contentious matter—or, perhaps more realistically, in reducing the risk of relapse during long-term abstinence in former tobacco users. Conceivably, an improved nano-vaccine might produce an even stronger immune response to further reduce nicotine’s discriminable and other addiction-related effects in nicotine-experienced subjects. Our results certainly support the continued development of novel nicotine nano-vaccines, either as a single approach or as a key element of a multimodal treatment strategy for smoking cessation.

FUNDING AND DISCLOSURE

The authors declare no conflict of interest.