Most smokers are aware of the dangers of smoking and want to quit, yet few are 
successful owing to the highly addictive properties of nicotine. Available 
smoking cessation tools include pharmacotherapies that act in the CNS and show 
modest long-term efficacy. Additionally, there are emerging concerns that they 
may cause adverse neuropsychiatric events. Antinicotine vaccines have been used 
experimentally as aids to smoking cessation. It is hypothesized that antibody 
capture of nicotine in the bloodstream would prevent it from crossing the 
blood-brain barrier and reaching the nicotinic receptors. The advantage of the 
approach includes the relatively gradual rise of antibody levels, which may 
reduce nicotine withdrawal symptoms, and the possible persistence of the 
antibodies potentially provides long-term protection, possibly preventing 
relapse. Proof-of-concept studies of at least two vaccine candidates have shown 
correlations between antinicotine antibody exposure and smoking abstinence. 
Unfortunately, the only vaccine tested in two large, randomized Phase III 
trials, 3'-amino-methyl-nicotine r-exoprotein A conjugate vaccine (NicVAX(®), 
Nabi Biopharmaceuticals, MD, USA), did not demonstrate efficacy. However, 
despite the lack of efficacy, there is good reason for continued optimism. This 
review will summarize the current status of the development of nicotine 
vaccines, discuss possible causes for the mixed results and review future 
scientific directions.