Vaccination against nicotine during continued nicotine administration in rats: immunogenicity of the vaccine and effects on nicotine distribution to brain

Vaccination against nicotine has been proposed as a potential treatment for nicotine dependence. Because vaccination may take months to elicit satisfa ctory antibody levels, the clinical usefulness of this approach will be enh anced if vaccination can be accomplished during continued nicotine intake ( e.g., before a smoker quits). The current study examined the immunogenicity of a nicotine conjugate vaccine during continued nicotine dosing in rats, and its effects on nicotine distribution to brain. In the first experiment, nicotine was administered over 11 weeks as 20 intra venous (i.v.) bolus in jections per day during the rat's active cycle to simulate the usual patter n of nicotine intake from cigarette smoking. Tn the second experiment, rats received a continuous s.c. infusion of nicotine by osmotic pump for ii wee ks to provide serum nicotine concentrations equivalent to those of a heavy smoker and 24 h/day nicotine exposure. Nicotine-specific antibody titers af ter the third booster dose were not compromised by either regimen of concur rent nicotine administration compared to those of rats receiving saline. A single additional i.v. nicotine dose was administered at the end of each ex periment. The distribution of this single nicotine dose to brain was reduce d by 40-60% in vaccinated rats compared to controls. Vaccine efficacy in re ducing nicotine distribution to brain was not compromised by concurrent nic otine administration. These data suggest that vaccination during concurrent nicotine administration is Feasible, and that the ability of vaccination t o reduce nicotine distribution to brain is preserved even after months of n icotine dosing at rates approximating cigarette smoking. (C) 2000 Internati onal Society for Immunopharmacology. Published by Elsevier Science Ltd. All rights reserved.