Combined active and passive immunization against nicotine: Minimizing monoclonal antibody requirements using a target antibody concentration strategy

• Published in: International immunopharmacology 2011-11, Vol.11 (11), p.1809-1815
• Main Authors: Cornish, Katherine E., Harris, Andrew C., LeSage, Mark G., Keyler, Dan E., Burroughs, Danielle, Earley, Cathy, Pentel, Paul R.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal - therapeutic use; Antibody Affinity - immunology; Antibody Formation - immunology; Biological and medical sciences; Brain - metabolism; Feasibility Studies; Immunization, Passive - methods; Immunotherapy; Locomotor sensitization; Male; Medical sciences; Monoclonal antibody; Motor Activity - drug effects; Nicotine; Nicotine - blood; Nicotine - immunology; Nicotine - metabolism; Pharmacokinetics; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Smoking - immunology; Smoking Cessation - methods; Smoking Prevention; Tissue Distribution; Vaccination - methods; Vaccine; Vaccines - administration & dosage; Vaccines - immunology
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2011.07.009

Nicotine vaccines have shown preliminary evidence of efficacy for enhancing smoking cessation rates, but the serum nicotine-specific antibody (NicAb) concentrations produced are highly variable and many subjects do not develop effective levels. As an alternative to vaccination, passive immunization with nicotine-specific monoclonal antibodies could produce more uniform serum NicAb concentrations, but its use is limited by their high cost and shorter elimination half-life. This study investigated supplementing vaccination with monoclonal antibodies in a targeted fashion to increase vaccine efficacy while minimizing the required monoclonal antibody dose. Rats were vaccinated and then given individualized supplemental doses of the nicotine-specific monoclonal antibody Nic311 to achieve a target total serum NicAb concentration known to be effective for blocking locomotor sensitization (LMS) to nicotine. Rats received vaccine, Nic311, both, or neither, followed by 0.3mg/kg nicotine s.c. for 10days to produce LMS. Combination immunotherapy completely blocked the development of LMS, while monotherapy with vaccine or Nic311 alone was only minimally effective. Lower brain nicotine levels were associated with reduced locomotor activity averaged over days 7–10. Despite its greater efficacy, combination immunotherapy did not reduce the variability in the resulting total serum NicAb concentrations. Variability in total serum NicAb concentrations was contributed to by both vaccine-generated antibody and by Nic311. These data show that combination immunotherapy, using a Nic311 dose that is by itself only minimally effective, can substantially enhance nicotine vaccine efficacy. However, variability in serum NicAb levels with combination immunotherapy may make translation of this approach challenging. ► Combination immunotherapy was studied to enhance nicotine vaccine efficacy. ► Vaccination was supplemented with a nicotine-specific monoclonal antibody. ► A target concentration strategy was used to minimize the required antibody dose. ► The combination of treatments attenuated locomotor sensitization to nicotine in rats. ► Combination immunotherapy was more effective than either therapy alone.