Effects of the Nanoparticle-Based Vaccine, SEL-068, on Nicotine Discrimination in Squirrel Monkeys.

A key feature of addiction to nicotine likely resides in its ability to produce subjective effects that, in turn, may be reflected in its discriminative-stimulus properties. Vaccination against such effects of nicotine offers an intriguing therapeutic approach for smoking cessation, but a reliably effective and immunologically safe vaccine remains to be identified. Here we report on the ability of SEL-068, a nanoparticle-based vaccine that targets nicotine, to modify the discriminative-stimulus effects of nicotine in a primate species. Results indicate that squirrel monkeys vaccinated with SEL-068 failed to acquire 0.1 mg/kg nicotine discrimination but readily learned to discriminate 0.001 mg/kg of the nicotinic full agonist (+)-epibatidine ((+)-EPI). After (+)-EPI training, doses of nicotine ⩾ 0.32 mg/kg, which produced behaviorally adverse actions, still failed to substitute for the (+)-EPI training stimulus in immunized monkeys, whereas (+)-EPI and the partial agonist varenicline engendered, respectively, complete and partial substitution in all monkeys with potency comparable to their potency in non-immunized subjects. In other subjects, nicotine was trained as a discriminative-stimulus and then replaced by (+)-EPI. Subsequent vaccination with SEL-068 led to a threefold and long-lasting (>30 weeks) decrease in the potency of nicotine but not (+)-EPI or varenicline. Collectively, our results show that SEL-068 can block the development of nicotine discrimination and attenuate nicotine's effects in nicotine-experienced monkeys without altering the discriminative-stimulus properties of other nicotinic drugs. The difference in the vaccine's effects in naive and nicotine-experienced subjects provides important insight into the conditions under which immunotherapy may be effective in combating nicotine addiction.