Cigarette smokers who are having trouble quitting because of nicotine's addictive power may some day be able to receive a novel antibody-producing vaccine to help them kick the habit.
The average cigarette contains about 4000 different chemicals that - when burned and inhaled - cause the serious health problems associated with smoking. But it is the nicotine in cigarettes that, like other addictive substances, stimulates rewards centers in the brain and hooks smokers to the pleasurable but dangerous routine.
Ronald Crystal, who chairs the department of genetic medicine at Weill-Cornell Medical College in New York, where researchers are developing a nicotine vaccine, said the idea is to stimulate the smoker's immune system to produce antibodies or immune proteins to destroy the nicotine molecule before it reaches the brain. But Crystal said nicotine antibodies are too small and don't last long enough in the bloodstream for the immune system to mount a sustained attack. So scientists took the DNA - the genetic building blocks - of the nicotine antibodies and used it to genetically modify the liver to continuously produce them.
The result, said Crystal, is a steady stream of antibodies circulating through the smoker's bloodstream, constantly on the lookout for nicotine molecules. Crystal likened the antibodies' behavior to the early video arcade game, Pacman, which involved an animated creature racing through a maze eating dots. In this case, each 'dot' is a nicotine molecule.
"These little Pacman antibodies then gobble it up and prevent it from reaching its receptors in the brain," he said. "And that's what gives the pleasure from smoking. So essentially [we are] blocking the nicotine from reaching the brain. And so you get no effect from the nicotine."
Researchers created the vaccine by taking the genetically-engineered nicotine antibody, inserting it into a harmless virus and directing the virus to infect the liver cells of laboratory mice. With the virus in their nuclei, the liver cells started producing nicotine antibodies, essentially bypassing the immune system and creating a new army of proteins to seek out and destroy any nicotine they might encounter.
"Once we genetically modify their livers to make an antibody against nicotine - so now the antibodies against nicotine are floating around in the blood - and we administer nicotine to the mouse, nothing happens. It's like they are getting water," Crystal added.
Using infrared beams to measure the activity level of the experimental mice, Crystal says nicotine-addicted mice that received the vaccine were just as alert as normal mice. The rodents were also more active than mice that received nicotine but not the vaccine. A single dose of the vaccine was effective for the life of the mice.
Ronald Crystal and colleagues report on their nicotine vaccine in the journal Science Translational Medicine.
The average cigarette contains about 4000 different chemicals that - when burned and inhaled - cause the serious health problems associated with smoking. But it is the nicotine in cigarettes that, like other addictive substances, stimulates rewards centers in the brain and hooks smokers to the pleasurable but dangerous routine.
Ronald Crystal, who chairs the department of genetic medicine at Weill-Cornell Medical College in New York, where researchers are developing a nicotine vaccine, said the idea is to stimulate the smoker's immune system to produce antibodies or immune proteins to destroy the nicotine molecule before it reaches the brain. But Crystal said nicotine antibodies are too small and don't last long enough in the bloodstream for the immune system to mount a sustained attack. So scientists took the DNA - the genetic building blocks - of the nicotine antibodies and used it to genetically modify the liver to continuously produce them.
The result, said Crystal, is a steady stream of antibodies circulating through the smoker's bloodstream, constantly on the lookout for nicotine molecules. Crystal likened the antibodies' behavior to the early video arcade game, Pacman, which involved an animated creature racing through a maze eating dots. In this case, each 'dot' is a nicotine molecule.
"These little Pacman antibodies then gobble it up and prevent it from reaching its receptors in the brain," he said. "And that's what gives the pleasure from smoking. So essentially [we are] blocking the nicotine from reaching the brain. And so you get no effect from the nicotine."
Researchers created the vaccine by taking the genetically-engineered nicotine antibody, inserting it into a harmless virus and directing the virus to infect the liver cells of laboratory mice. With the virus in their nuclei, the liver cells started producing nicotine antibodies, essentially bypassing the immune system and creating a new army of proteins to seek out and destroy any nicotine they might encounter.
"Once we genetically modify their livers to make an antibody against nicotine - so now the antibodies against nicotine are floating around in the blood - and we administer nicotine to the mouse, nothing happens. It's like they are getting water," Crystal added.
Using infrared beams to measure the activity level of the experimental mice, Crystal says nicotine-addicted mice that received the vaccine were just as alert as normal mice. The rodents were also more active than mice that received nicotine but not the vaccine. A single dose of the vaccine was effective for the life of the mice.
Ronald Crystal and colleagues report on their nicotine vaccine in the journal Science Translational Medicine.
