BACKGROUND: By reducing the amount of nicotine that reaches the brain when a 
person smokes a cigarette, nicotine vaccines may help people to stop smoking or 
to prevent recent quitters from relapsing.
OBJECTIVES: The aims of this review are to assess the efficacy of nicotine 
vaccines for smoking cessation and for relapse prevention, and to assess the 
frequency and type of adverse events associated with the use of nicotine 
vaccines.
SEARCH METHODS: We searched the Cochrane Tobacco Addiction Review Group 
specialised register for trials, using the term 'vaccine' in the title or 
abstract, or in a keyword (date of most recent search April 2012). To identify 
any other material including reviews and papers potentially relevant to the 
background or discussion sections, we also searched MEDLINE, EMBASE, and 
PsycINFO, combining terms for nicotine vaccines with terms for smoking and 
tobacco use, without design limits or limits for human subjects. We searched the 
Annual Meeting abstracts of the Society for Research on Nicotine and Tobacco up 
to 2012, using the search string 'vaccin'. We searched Google Scholar for 
'nicotine vaccine'. We also searched company websites and Google for information 
related to specific vaccines. We searched clinicaltrials.gov in March 2012 for 
'nicotine vaccine' and for the trade names of known vaccine candidates.
SELECTION CRITERIA: We included randomized controlled trials of nicotine 
vaccines, at Phase II and Phase III trial stage and beyond, in adult smokers or 
recent ex-smokers. We included studies of nicotine vaccines used as part of 
smoking cessation or relapse prevention interventions.
DATA COLLECTION AND ANALYSIS: We extracted data on the type of participants, the 
dose and duration of treatment, the outcome measures, the randomization 
procedure, concealment of allocation, blinding of participants and personnel, 
reporting of outcomes, and completeness of follow-up.Our primary outcome measure 
was a minimum of six months abstinence from smoking. We used the most rigorous 
definition of abstinence, and preferred cessation rates at 12 months and 
biochemically validated rates where available. We have used the risk ratio (RR) 
to summarize individual trial outcomes. We have not pooled the current group of 
included studies as they cover different vaccines and variable regimens.
MAIN RESULTS: There are no nicotine vaccines currently licensed for public use, 
but there are a number in development. We found four trials which met our 
inclusion criteria, three comparing NicVAX to placebo and one comparing NIC002 
(formerly NicQbeta) to placebo. All were smoking cessation trials conducted by 
pharmaceutical companies as part of the drug development process, and all trials 
were judged to be at high or unclear risk of bias in at least one domain. 
Overall, 2642 smokers participated in the included studies in this review. None 
of the four included studies detected a statistically significant difference in 
long-term cessation between participants receiving vaccine and those receiving 
placebo. The RR for 12 month cessation in active and placebo groups was 1.35 
(95% Confidence Interval (CI) 0.82 to 2.22) in the trial of NIC002 and 1.74 (95% 
CI 0.73 to 4.18) in one NicVAX trial. Two Phase III NicVAX trials, for which 
full results were not available, reported similar quit rates of approximately 
11% in both groups. In the two studies with full results available, post hoc 
analyses detected higher cessation rates in participants with higher levels of 
nicotine antibodies, but these findings are not readily generalisable. The two 
studies with full results showed nicotine vaccines to be well tolerated, with 
the majority of adverse events classified as mild or moderate. In the study of 
NIC002, participants receiving the vaccine were more likely to report mild to 
moderate adverse events, most commonly flu-like symptoms, whereas in the study 
of NicVAX there was no significant difference between the two arms. Information 
on adverse events was not available for the large Phase III trials of 
NicVAX.Vaccine candidates are likely to undergo significant changes before 
becoming available to the general public, and those included in this review may 
not be the first to reach market; this limits the external validity of the 
results reported in this review in terms of both effectiveness and tolerability.
AUTHORS' CONCLUSIONS: There is currently no evidence that nicotine vaccines 
enhance long-term smoking cessation. Rates of serious adverse events recorded in 
the two trials with full data available were low, and the majority of adverse 
events reported were at mild to moderate levels. The evidence available suggests 
nicotine vaccines do not induce compensatory smoking or affect withdrawal 
symptoms. No nicotine vaccines are currently licensed for use in any country but 
a number are under development.Further trials of nicotine vaccines are needed, 
comparing vaccines with placebo for smoking cessation. Further trials are also 
needed to explore the potential of nicotine vaccines to prevent relapse. Results 
from past, current and future research should be reported in full. Adverse 
events and serious adverse events should continue to be carefully monitored and 
thoroughly reported.