Preclinical development of a vaccine 'against smoking'.
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.
Cerny
E H
EH
Chilka Ltd, Lausanne, Switzerland.
Lévy
R
R
Mauel
J
J
Mpandi
M
M
Mutter
M
M
Henzelin-Nkubana
C
C
Patiny
L
L
Tuchscherer
G
G
Cerny
T
T
D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology*; D002772:Cholera Toxin / Q000276:immunology*; D005260:Female; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007260:Infusion Pumps; D051379:Mice; D008807:Mice, Inbred BALB C; D009538:Nicotine / Q000276:immunology*; D012907:Smoking / Q000276:immunology; D016540:Smoking Cessation / Q000379:methods*; D000074606:Smoking Prevention; D014029:Tobacco Use Disorder / Q000276:immunology / Q000517:prevention & control*; D014614:Vaccines, Synthetic / Q000276:immunology*
D002352:Carrier Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic; D009538:Nicotine; D002772:Cholera Toxin