Literature DB >> 12415193

Preclinical development of a vaccine 'against smoking'.

E H Cerny1, R Lévy, J Mauel, M Mpandi, M Mutter, C Henzelin-Nkubana, L Patiny, G Tuchscherer, T Cerny.   

Abstract

BACKGROUND: Nicotine is the main culprit for dependence on tobacco-containing products, which in turn are a major etiologic factor for cardiovascular diseases and cancer. This publication describes a vaccine, which elicits antibodies against nicotine. The antibodies in the blood stream intercept the nicotine molecule on its way to its receptors and greatly diminish the nicotine influx to the brain shortly after smoking.
METHODS: The nicotine molecule is chemically linked to cholera toxin B as a carrier protein in order to induce antibodies. The potential to elicit antibodies after subcutaneous as well as intranasal immunization is evaluated. In order to simulate realistic conditions, nicotine pumps delivering the nicotine equivalent of 5 packages of cigarettes for 4 weeks are implanted into the mice 1 week prior to vaccination. The protective effect of the vaccine is measured 5 weeks after vaccination by comparing the influx of radiolabeled nicotine in the brains of vaccinated and non-vaccinated animals 5 min after challenge with the nicotine equivalent of 2 cigarettes.
RESULTS: The polyclonal antibodies induced by the vaccine show a mean avidity of 1.8 x 10(7) l/Mol. Subcutaneous immunization elicits high antibody levels of the IgG class, and significant IgA antibody levels in the saliva of vaccinated mice can be found after intranasal vaccination. The protective effect also in the animals with implanted nicotine pumps is significant: less than 10% of radiolabeled nicotine found in the brains of non-vaccinated animals can be found in the brains of vaccinated animals.
CONCLUSIONS: These data provide credible evidence that a vaccine can break the vicious circle between smoking and instant gratification by intercepting the nicotine molecule. Astonishingly, there is no sign of exhaustion of specific antibodies even under extreme conditions, which makes it highly unlikely that a smoker can overcome the protective effect of the vaccine by smoking more. Finally, the high titers of specific antibodies after 1 year let us hope that booster vaccinations are probably only necessary in intervals of years. Copyright 2002 S. Karger GmbH, Freiburg

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Year:  2002        PMID: 12415193     DOI: 10.1159/000067433

Source DB:  PubMed          Journal:  Onkologie        ISSN: 0378-584X


  24 in total

1.  Effects of a nicotine conjugate vaccine on the acquisition and maintenance of nicotine self-administration in rats.

Authors:  Mark G LeSage; Daniel E Keyler; Yoko Hieda; Greg Collins; Danielle Burroughs; Chap Le; Paul R Pentel
Journal:  Psychopharmacology (Berl)       Date:  2005-07-01       Impact factor: 4.530

Review 2.  Current status of immunologic approaches to treating tobacco dependence: vaccines and nicotine-specific antibodies.

Authors:  Mark G LeSage; Daniel E Keyler; Paul R Pentel
Journal:  AAPS J       Date:  2006-02-24       Impact factor: 4.009

3.  Vaccines to combat smoking.

Authors:  Rick A Bevins; Jamie L Wilkinson; Sam D Sanderson
Journal:  Expert Opin Biol Ther       Date:  2008-04       Impact factor: 4.388

4.  Increased efficacy of a trivalent nicotine vaccine compared to a dose-matched monovalent vaccine when formulated with alum.

Authors:  Sabina H L de Villiers; Katherine E Cornish; Andrew J Troska; Marco Pravetoni; Paul R Pentel
Journal:  Vaccine       Date:  2013-10-29       Impact factor: 3.641

Review 5.  Adjuvants for vaccines to drugs of abuse and addiction.

Authors:  Carl R Alving; Gary R Matyas; Oscar Torres; Rashmi Jalah; Zoltan Beck
Journal:  Vaccine       Date:  2014-08-08       Impact factor: 3.641

6.  A methamphetamine vaccine attenuates methamphetamine-induced disruptions in thermoregulation and activity in rats.

Authors:  Michelle L Miller; Amira Y Moreno; Shawn M Aarde; Kevin M Creehan; Sophia A Vandewater; Brittani D Vaillancourt; M Jerry Wright; Kim D Janda; Michael A Taffe
Journal:  Biol Psychiatry       Date:  2012-10-23       Impact factor: 13.382

7.  Effect of a nicotine vaccine on nicotine binding to β2*-nicotinic acetylcholine receptors in vivo in human tobacco smokers.

Authors:  Irina Esterlis; Jonas O Hannestad; Evgenia Perkins; Frederic Bois; D Cyril D'Souza; Rachel F Tyndale; John P Seibyl; Dorothy M Hatsukami; Kelly P Cosgrove; Stephanie S O'Malley
Journal:  Am J Psychiatry       Date:  2013-04       Impact factor: 18.112

8.  Suppression of nicotine-induced pathophysiology by an adenovirus hexon-based antinicotine vaccine.

Authors:  Jonathan B Rosenberg; Bishnu P De; Martin J Hicks; Kim D Janda; Stephen M Kaminsky; Stefan Worgall; Ronald G Crystal
Journal:  Hum Gene Ther       Date:  2013-06       Impact factor: 5.695

Review 9.  Immunopharmacotherapy: vaccination strategies as a treatment for drug abuse and dependence.

Authors:  Amira Y Moreno; Kim D Janda
Journal:  Pharmacol Biochem Behav       Date:  2009-04       Impact factor: 3.533

10.  Enhancing nicotine vaccine immunogenicity with liposomes.

Authors:  Jonathan W Lockner; Sam On Ho; Karen C McCague; Su Ming Chiang; Thai Q Do; Gary Fujii; Kim D Janda
Journal:  Bioorg Med Chem Lett       Date:  2012-12-27       Impact factor: 2.823

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