A Vaccine against Nicotine for Smoking Cessation: A Randomized Controlled Trial

Abstract

BackgroundTobacco dependence is the leading cause of preventable death and disabilities worldwide and nicotine is the main substance responsible for the addiction to tobacco. A vaccine against nicotine was tested in a 6-month randomized, double blind phase II smoking cessation study in 341 smokers with a subsequent 6-month follow-up period.Methodology/Principal Findings229 subjects were randomized to receive five intramuscular injections of the nicotine vaccine and 112 to receive placebo at monthly intervals. All subjects received individual behavioral smoking cessation counseling. The vaccine was safe, generally well tolerated and highly immunogenic, inducing a 100% antibody responder rate after the first injection. Point prevalence of abstinence at month 2 showed a statistically significant difference between subjects treated with Nicotine-Qβ (47.2%) and placebo (35.1%) (P = 0.036), but continuous abstinence between months 2 and 6 was not significantly different. However, in subgroup analysis of the per-protocol population, the third of subjects with highest antibody levels showed higher continuous abstinence from month 2 until month 6 (56.6%) than placebo treated participants (31.3%) (OR 2.9; P = 0.004) while medium and low antibody levels did not increase abstinence rates. After 12 month, the difference in continuous abstinence rate between subjects on placebo and those with high antibody response was maintained (difference 20.2%, P = 0.012).ConclusionsWhereas Nicotine-Qβ did not significantly increase continuous abstinence rates in the intention-to-treat population, subgroup analyses of the per-protocol population suggest that such a vaccination against nicotine can significantly increase continuous abstinence rates in smokers when sufficiently high antibody levels are achieved. Immunotherapy might open a new avenue to the treatment of nicotine addiction.Trial RegistrationSwiss Medical Registry 2003DR2327; ClinicalTrials.gov NCT00369616

Crystal structures of a therapeutic single chain antibody in complex with two drugs of abuse—Methamphetamine and 3,4‐methylenedioxymethamphetamine

“…This approach is showing promising results in early clinical trials for the treatment of nicotine and cocaine addiction. 2,3 Passive immunization for drug abuse involves intravenous delivery of a bioengineered antidrug monoclonal antibody (mAbs) or a fragment such as Fab or single chain variable fragment (scFv) (Fig. 1) to attain immediate short term (minutes to hours) or long-lasting (weeks to months) protection.…”

“…The drugs in this report likely interact with fewer residues because of their smaller surface area and paucity of charged atoms in the molecules. METH surface area is calculated as 206 Å 2 and it has only one charged atom available for hydrogen bonding at physiological pH ($7.4). Therefore, an anti-METH mAb has only a limited number of potential interaction sites for optimizing specificity and affinity.…”

Ethical and policy issues in using vaccines to treat and prevent cocaine and nicotine dependence

“…Those in the top third of responders had higher abstinence rates at the 6 and 12-month follow-ups (see Table 1) [38]. follow-ups than those on placebo.…”

The International Primary Care Respiratory Group (IPCRG) Research Needs Statement 2010

“…241 Nicotine vaccines are under development, and may offer an additional option especially for preventing relapse. [242][243][244] Primary care teams can review their patients' progress and offer on-going support, though it is not clear which strategies are most effective in preventing relapse. 245 …”