1 / 36

Nicotine Vaccines

Nicotine Vaccines. 6 Nicotine vaccines studied in animals 2 Nicotine vaccines in Phase I clinical trials Other vaccines Cocaine: phase II clinical trial Phencyclidine Methamphetamine. Targeting the Drug Rather Than the Brain. Brain. Blood. +. Nicotine Immunogen Structure. Linker.

cisco
Download Presentation

Nicotine Vaccines

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Nicotine Vaccines • 6 Nicotine vaccines studied in animals • 2 Nicotine vaccines in Phase I clinical trials • Other vaccines • Cocaine: phase II clinical trial • Phencyclidine • Methamphetamine

  2. Targeting the Drug Rather Than the Brain

  3. Brain Blood +

  4. Nicotine Immunogen Structure Linker Carrier Protein Nicotine

  5. Nicotine Immunogen Structure Linker Carrier Protein Nicotine • Smokers don’t have nicotine antibodies • Smoking won’t boost or maintain antibody titers • Boosting requires administration of immunogen

  6. 1-2 months

  7. Brain Blood +

  8. Vaccine Effects on Nicotine Distribution 1 Minute after Nicotine 0.1 mg/kg i.v. Satoskar et al, CPDD 2000

  9. Vaccine Effects on Nicotine Distribution 1 Minute after Nicotine 0.1 mg/kg i.v. Satoskar et al, CPDD 2000

  10. Vaccine Effects on Nicotine Distribution Chronic Infusion 1 mg/kg/d + Acute Dose 0.03 mg/kg * * Hieda Y et al, Int J Immunopharmacol 2002;22:809

  11. Effects of Antibody Titer onBrain Nicotine Concentration 1.5 Serum Antibody Concentration (ELISA O.D.) 1.0 100 150 50 Brain Nicotine (ng/g)

  12. 1000 Vaccine Control 100 Serum Nicotine (ng/ml) 10 1 0 2 4 6 8 10 12 Hours Vaccine Effects on Nicotine Elimination Keyler D et al, Nicotine Tobacco Res 1999;1:241

  13. Passive Immunization Blocks Nicotine-Induced Increases in Blood Pressure Pentel et al. Pharmacol Biochem Behav 2000;65:191

  14. Passive Immunization Attenuates Nicotine Discrimination Malin et al. Life Sci 2002;70:2793

  15. 90 80 * * 70 60 50 Abstinence Signs (% of pre-treatment) 40 30 20 10 0 Control IgG Control IgG Nicotine IgG Saline Nicotine Nicotine Passive Immunization Attenuates Nicotine-Induced Relief of Nicotine Withdrawal Malin DH et al. Pharmacol Biochem Behav 2001;68:87

  16. Vaccine Effects on the Acquisition of Nicotine Self-Administration0.01 mg/kg/dose Mean Infusions

  17. Vaccination Attenuates the Reinstatement of Nicotine Responding Control Vaccine Lindblom et al. Resp 2002; 69:254

  18. Antibody Response10 ug Immunogen x 4 in Smokers Absorbance 0 2 4 6 8 10 12 Weeks St. Clair Roberts et al. CPDD 2002

  19. Antibody Titer after a Single Dose of Nicotine Conjugate Vaccine Reciprocal Endpoint Dilution Days Lindmayer, K et al, European SRNT 2002

  20. Cocaine Vaccine Persistence of Antibody Titers Kosten et al. Vaccine 2002;20:1196

  21. Perspective • Uses • Decrease reward: cessation, relapse (direct nicotine effects) • Not for craving or withdrawal (neuroadaptive processes)

  22. Perspective • Uses • Decrease reward: cessation, relapse (direct nicotine effects) • Not for craving or withdrawal (neuroadaptive processes) • Attractive features • Infrequent dosing, long duration  compliance • Novel mechanism: combine with other medications • Safety/side effects

  23. Perspective • Uses • Decrease reward: cessation, relapse (direct nicotine effects) • Not for craving or withdrawal (neuroadaptive processes) • Attractive features • Infrequent dosing, long duration  compliance • Novel mechanism: combine with other medications • Safety/side effects • Limitations • Need high titers of antibody • Individual variability • Slow onset • Compensation

  24. Perspective • Uses • Decrease reward: cessation, relapse (direct nicotine effects) • Not for craving or withdrawal (neuroadaptive processes) • Attractive features • Infrequent dosing, long duration  compliance • Novel mechanism: combine with other medications • Safety/side effects • Limitations • Need high titers of antibody • Individual variability Passive Immunization • Slow onset • Compensation

  25. Future Directions • Mechanisms • High drug:antibody ratio, role of  nicotine elimination • Maximizing antibody titers • Carrier protein, adjuvants, schedules • Vaccination v. passive immunization • Complementary roles • Combinations of therapies • Medications, counseling • Safety • Pregnancy

  26. Passive Immunization Blocks Cocaine Self-Administration Infusions per hour Fox BS et al. Nature Medicine 1996;2:1129

  27. VaccinesInfectious Diseases v. Drug Dependence • Infectious diseases • Bind pathogen immune response  kill pathogen • Effects: often complete, long-lasting protection • Drug dependence • Bind drug  alter pharmacokinetics  attenuate drug effect • Effects: dose-related, partial, selective, duration of months • Actions resemble a medication more than a vaccine

  28. PASSIVE IMMUNIZATION ATTENUATES NICOTINE-INDUCED RELIEF OF NICOTINE WITHDRAWAL * * Abstinence Signs (% of pre-treatment) Malin DH et al. Pharmacol Biochem Behav 2001;68:87

  29. Effects of Antibody Titer onBrain Nicotine Concentration 1.5 ELISA O.D. 1.0 100 150 50 Brain Nicotine (ng/g)

  30. Nicotine VaccinesTargeting the Drug Rather Than the Brain • Rationale • Mechanism of action • Animal data • Clinical trials • Practical points • Perspective • Future directions

  31. Comparison of Vaccination Regimens Absorbance 0 2 4 6 8 12 10 Weeks St. Clair Roberts et al. CPDD 2002

  32. Passive Immunization Blocks Nicotine-Induced Increases in Locomotor Activity Pentel et al. Pharmacol Biochem Behav 2000;65:191

  33. 90 80 * * 70 Abstinence Signs (% of pre-treatment) 60 50 40 30 20 10 0 Control IgG Control IgG Nicotine IgG Saline Nicotine Nicotine Passive Immunization Attenuates Nicotine-Induced Relief of Nicotine Withdrawal Malin DH et al. Pharmacol Biochem Behav 2001;68:87

More Related