Nicotine Vaccines - PowerPoint PPT Presentation

Loading...

PPT – Nicotine Vaccines PowerPoint presentation | free to view - id: f2ace-ZDc1Z



Loading


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation
Title:

Nicotine Vaccines

Description:

Passive Immunization Attenuates Nicotine-Induced Relief of Nicotine Withdrawal ... Bind drug alter pharmacokinetics attenuate drug effect ... – PowerPoint PPT presentation

Number of Views:100
Avg rating:3.0/5.0
Slides: 37
Provided by: jennife387
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: Nicotine Vaccines


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
Blood
Brain

4
Nicotine Immunogen Structure
Linker
Carrier Protein
Nicotine
5
Nicotine Immunogen Structure
Linker
Carrier Protein
Nicotine
  • Smokers dont have nicotine antibodies
  • Smoking wont boost or maintain antibody titers
  • Boosting requires administration of immunogen

6
1-2 months
7
Blood
Brain

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 200222809
11
Effects of Antibody Titer onBrain Nicotine
Concentration
1.5
Serum Antibody Concentration (ELISA O.D.)
1.0
150
100
50
Brain Nicotine (ng/g)
12
Vaccine Effects on Nicotine Elimination
Keyler D et al, Nicotine Tobacco Res 19991241
13
Passive Immunization Blocks
Nicotine-Induced Increases in Blood Pressure
Pentel et al. Pharmacol Biochem Behav 200065191
14
Passive Immunization Attenuates Nicotine
Discrimination
Malin et al. Life Sci 2002702793
15
Passive Immunization Attenuates
Nicotine-Induced Relief of Nicotine Withdrawal
Malin DH et al. Pharmacol Biochem Behav 20016887
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 69254
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 2002201196
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 drugantibody 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
(No Transcript)
27
(No Transcript)
28
Passive Immunization Blocks Cocaine
Self-Administration
Infusions per hour
Fox BS et al. Nature Medicine 199621129
29
(No Transcript)
30
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

31
PASSIVE IMMUNIZATION ATTENUATES
NICOTINE-INDUCED RELIEF OF NICOTINE
WITHDRAWAL


Abstinence Signs ( of pre-treatment)
Malin DH et al. Pharmacol Biochem Behav 20016887
32
Effects of Antibody Titer onBrain Nicotine
Concentration
1.5
ELISA O.D.
1.0
150
100
50
Brain Nicotine (ng/g)
33
Nicotine VaccinesTargeting the Drug Rather Than
the Brain
  • Rationale
  • Mechanism of action
  • Animal data
  • Clinical trials
  • Practical points
  • Perspective
  • Future directions

34
Comparison of Vaccination Regimens
Absorbance
0
2
4
6
8
12
10
Weeks
St. Clair Roberts et al. CPDD 2002
35
Passive Immunization Blocks
Nicotine-Induced Increases in Locomotor Activity
Pentel et al. Pharmacol Biochem Behav 200065191
36
Passive Immunization Attenuates
Nicotine-Induced Relief of Nicotine Withdrawal
Malin DH et al. Pharmacol Biochem Behav 20016887
About PowerShow.com