Smoking is a global healthcare problem. Current smoking cessation rates using 
behavioral counseling and pharmacotherapeutic interventions have had modest 
success, with ∼1:5 smokers remaining abstinent long-term. Nicotine vaccines are 
a new class of immunotherapeutics under development. It is believed that 
anti-nicotine antibodies arising from vaccination capture nicotine and prevent 
or reduce its entry into the brain, as the antibody-bound nicotine is too large 
to cross the blood-brain barrier. This in turn decreases the pleasurable effects 
of smoking, reducing or eliminating positive reinforcement, thereby making it 
easier for a smoker to quit smoking. Four vaccine candidates have advanced into 
clinical testing with mixed success. Proof-of-concept has been established in 
that individuals with higher levels of anti-nicotine antibodies were observed to 
have higher smoking cessation and abstinence rates. Recently, the most advanced 
candidate vaccine, NicVAX, failed to meet the primary endpoint in two large 
phase III studies, although the correlation of higher abstinence rates in 
subjects with higher immunity to nicotine was observed. Although the field has 
had setbacks, the magnitude of the tobacco epidemic and the positive 
pre-clinical research and observed clinical trends indicate continued research 
is warranted. Several avenues are being actively pursued: a) improving vaccine 
potency by introducing novel carriers and/or adjuvants to stimulate higher 
immune response b) targeting subjects who have a robust response (e.g. 
personalized medicine) c) combining vaccines with pharmacotherapy for 
maintenance of abstinence/relapse prevention.