Vice vaccines: scientists give a shot in the arm to the fight against smoking, drug abuse, and obesity

Science News,  Feb 10, 2007  by Christen Brownlee

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When Rachel Harrison was 16 years old, she took a drag from her first cigarette. She remembers loving it right away--the taste, the warmth, and especially the lightheaded rush that smoking gave her. Like a bad character in an after-school special, she chain-smoked an entire pack that first time while hanging out with other smokers from the popular crowd.

"I know it sounds cliche, but I started smoking because all the cool kids were doing it," says Harrison, now 32.

From high school through college, and now in her job as a public relations professional in New York, Harrison has kept up the habit. Nowadays, she paces her smoking to three or four cigarettes each workday. The weekends are a "free-for-all," she says, when she goes through often more than a pack a day.

But even though some part of her still loves each smoke as much as her first one, Harrison says, she longs to escape cigarettes' fiery grip. In her quest to avoid the bad breath, wrinkles, and cancer that smoking can bring, she guesses that she's tried to quit about 30 times in the past 15 years. But no matter which method she's used--nicotine gum, the patch, or just quitting cold turkey--she's never succeeded.

"I come back to it usually because a friend will be smoking and I'll ask for a drag," Harrison says. "That first drag will taste so disgusting, but for some reason, literally an hour later I'm asking for a full cigarette, then buying a new pack."

Soon, Harrison and other people plagued by some of Western societies' hardest-to-kick habits may literally get a shot in the arm: vaccines to help them quit. Vaccinations have long had a starring role in preventing a variety of diseases. But now, researchers are aiming the needle at a new set of targets--smoking, obesity, and illicit drugs. These vaccines, currently in development, could give people a novel way to boost their health and vanquish their vices.

SMOKE OUT Vaccines have been doing their part to eradicate disease since the 18th century, typically by jump-starting the immune system to fight infectious bacteria and viruses such as those that cause the flu, cholera, or tetanus. But in 1974, narcotics researcher C. Robert Schuster, then at the University of Chicago, and his colleagues published the first evidence that vaccines could rev up the immune system against a different type of target--heroin. In a twist on their typical preventive role, these vaccines stop substances from satisfying an already-addicted user's cravings.

Normally, the immune system doesn't recognize heroin and other drugs as foes worthy of attack. That's because drug molecules are significantly smaller than the foreign proteins on bacteria and viruses that trigger the body to defend itself, says immunologist Michael Owens of the University of Arkansas for Medical Sciences in Little Rock.

"In general, the cutoff in size for the immune system to recognize something as foreign will be about 10,000 daltons in weight. Most drugs of abuse are less than 500 [daltons]," he says. One dalton is about the weight of a single hydrogen atom.

To get the immune system fired up to fight heroin, Schuster and his team decided to make a vaccine by attaching heroin molecules to something that reliably triggers a response in healthy people and other animals. They used a protein from cows' blood. When the immune system senses the large, foreign protein with drug molecules piggybacked onto them, it pumps out a variety of antibodies, explains Owen. Some antibodies recognize pieces of the protein, but others home in on the drug.

"The small drug molecules are just along for the ride," adds vaccine researcher Kim Janda of the Scripps Research Institute in La Jolla, Calif., but the immune system generates antibodies against them nonetheless.

After Schuster's team gave the vaccine to heroin-addicted rhesus monkeys that could self-administer the drug by pushing a lever, the animals did so significantly less often than they had previously. The researchers hypothesized that the vaccine somehow prevented the monkeys from getting high, taking away their incentive to keep using the drug.

However, notes Owens, the idea of vaccinating against illegal drugs didn't immediately catch on. Methadone, a drug that satisfies heroin's cravings without causing a high, was already in use in the 1970s for treating heroin addiction, and Schuster's team wasn't seeing as strong an effect with its vaccine.

Over the next few decades, however, researchers began to see the value of Schuster's approach for treating other types of addiction. For example, vaccines to help smokers such as Harrison quit are now advancing through clinical trials.

One of these vaccines, called NieVax and manufactured by Nabi Biopharmaceuticals in Boca Raton, Fla., works by attaching multiple nicotine molecules to a protein taken from Pseudomonas aeruginosa, a species of bacteria that occasionally infects people.

When a smoker lights up and draws the addictive drug into his or her bloodstream, antibodies glom on to individual nicotine molecules, explains Nabi scientist Henrik Rasmussen. As a result, the formerly tiny molecules morph into clumps made of nicotine and antibodies. Those clusters are far too big to cross the blood-brain barrier and stimulate the brain's feel-good centers, an action that normally cements nicotine's addictive power.