Data from human studies discussing the pharmacokinetic properties of the 3′-AmNicrEPA vaccine are limited. A phase II immunogenicity and safety trial administered the vaccine to subjects at baseline, 1 month, 2 months, and 6 months. After the first intramuscular injection of 3′-AmNic-rEPA 200 μg, nicotine-specific antibodies were detected in participants within 14 days of administration. Peak nicotine-specific antibody concentrations were reached approximately 2 weeks after the third 200-μg injection, correlating with a geometric mean nicotine-specific antibody concentration greater than 30 μg/ml (Figure 2). A pharmacokinetic study assessing another nicotine vaccine (CYT002-NicQb [also known as nicotine-Qbeta]; Cytos Biotechnology, Zurich, Switzerland, and Novartis Pharmaceuticals, Basel, Switzerland), which has a slightly different formulation from that of the 3′- AmNic-rEPA vaccine, determined that in healthy volunteers the half-life of nicotine-specific antibodies in the absence of the adjuvant, alum, was 47 days compared with 67 days in those individuals receiving the vaccine containing alum.
Mean antibody concentration by 3′-AmNic-rEPA dose or placebo over time. Arrows indicate injection times; dashed line indicates target nicotine-specific antibody concentration necessary to maximize vaccine efficacy. No antibody response was generated by placebo at any point during the study. IgG = immunoglobulin G. (Adapted from reference 14 with permission.)
Affinity of 3′-AmNic-rEPA for nicotine in the serum is high. An animal study demonstrated the mean ±; SD percentage of bound nicotine in the serum for animals receiving the 3′-AmNicrEPA vaccine was 94 ±;11% compared with 11 ±; 8% for the control group. The unbound nicotine level in the serum in animals injected with the 3′-AmNic-rEPA vaccine was 5.1 ±3.2 ng/ml versus 17.7 ±3.8 ng/ml in controls (p<0.001). Animal models have shown that the elimination half-life of nicotine is prolonged by 3–6-fold in those who have been vaccinated, allowing nicotine levels to decrease more gradually. The nicotine vaccine is capable of reducing nicotine distribution to the brain by up to 65%.
Response to the 3′-AmNic-rEPA vaccine is maximized in those patients who are able to achieve high nicotine-specific antibody concentrations. Reference standards to classify nicotine antibody levels as high or low have been developed based on data from clinical trials. An antibody concentration greater than 25 μg/ml has been set as the optimal target for patients to achieve in order to enhance vaccine efficacy. Data from a recent trial demonstrated that in patients receiving the 400-μg dose of the vaccine in each of five injections, antibody concentrations decreased below the 25-μg/ml threshold at study week 40, approximately 15 weeks after the fifth injection. Despite a decline in therapeutic levels of antibodies, 6-month and 12-month abstinence rates were similar (17.6% and 15.7%, respectively).
Pharmacotherapy. 2011;31(7):703-713. © 2011 Pharmacotherapy Publications
Cite this: Nicotine Conjugate Vaccine as a Novel Approach to Smoking Cessation - Medscape - Jul 01, 2011.