Need to quit a bad habit? There could soon be a vaccine to help

CHICAGO — Vaccines, the most potent medical weapon devised to vanquish deadly germs, are being called on to do something different and culturally revolutionary: inoculate people against bad habits such as overeating, cigarette smoking and drug use.

Whether this new era of vaccine research can subdue many of the poor lifestyle choices that are today's biggest threats to health — causing obesity, cancer, heart disease and other problems — has yet to be proved.

But the evidence is promising enough to persuade the federal government to put millions of dollars toward finding out if two of the vaccines can end nicotine and cocaine addiction.

The National Institute on Drug Abuse, which has spent $15 million on clinical trials for the vaccines and plans to spend more, predicts that one of the nicotine vaccines may be available for marketing in three years.

"The American Cancer Society has projected that we will have 1 billion people die from smoking in the world in this century," said Frank Vocci, director of medications development for the institute. "If you had a vaccine that helped people quit and stay quit, or prevent them from smoking, that's where you'd get the greatest public-health benefit."

Meanwhile, results from a major obesity-vaccine trial in Switzerland are expected this year. The vaccine could be ready for use in a few years.

To tamp out deleterious behavior, the new vaccines employ the body's immune system in an innovative way. Instead of building antibodies to destroy germs as traditional vaccines do, they construct antibodies that lock onto nicotine and cocaine molecules, preventing them from reaching the brain.

"What we're seeing is a renaissance in vaccine technology," said Dr. Gary Nabel, director of the National Institute of Allergy and Infectious Diseases' Vaccine Research Center. "It's only natural that when you have a technology that's this powerful it can be applied to other medical problems."

Normally, nicotine and cocaine molecules are too small to be seen by the immune system. So to make the vaccines, scientists attach these molecules to big target proteins, such as harmless viruses or bacteria, which the immune system can recognize and attack with specialized antibodies.

When the person later smokes a cigarette or takes cocaine, the antibodies wrap up and neutralize the molecules before they can trigger feelings of euphoria and pleasure in the brain. Smokers and cocaine users given the vaccines say their pleasure is diminished or they no longer get as high, which decreases the desire for the drug.

In the case of the obesity vaccine, antibodies attach to the hunger hormone, ghrelin, preventing it from reaching the brain and stimulating appetite.

Ghrelin, which is secreted by the empty stomach, travels in the bloodstream to the brain, where it tells a person to eat. But the hormone, discovered in 1999, also has other important roles, such as signaling the body to become less active and to store food as fat instead of using it for energy production.

The reason it can be so hard to lose weight, researchers think, is that dieting causes large amounts of ghrelin to be produced as the body seeks to stimulate eating, slow the metabolism of fat and promote fat retention. Ghrelin also may help explain the yo-yo experience of millions who try to lose weight but end up gaining it.

"What happens after many attempts at dieting is that you lose weight but as soon as you stop dieting and go back on normal feeding your ghrelin levels rise again and that makes you have a lot of hunger," said immunologist Claudine Blaser, of the Swiss company Cytos, whose obesity vaccine is undergoing clinical trials in 100 people.

In experiments with mice, those who were given the vaccine reduced their weight gain by 15 percent to 20 percent even though they ate as much as other mice that became obese. Researchers also found they burned off more fat.

Cytos is also in advanced stages of testing a nicotine vaccine. Earlier studies showed that 42 percent of smokers receiving the vaccine remained abstinent after a year, compared with 21 percent who got a placebo shot.

"What we can do with our vaccine approach is to basically help these people get off their bad habits and get off their risks of developing severe chronic diseases later on," Blaser said.

The U.S. Food and Drug Administration recently put another nicotine vaccine, NicVAX, on a fast-track status so it can be rushed to market if shown to be safe and effective. Nabi Biopharmaceuticals, in Boca Raton, Fla., is expanding trials of NicVAX after an earlier study showed 40 percent of the people getting the vaccine were smoke-free after six months, compared with 9 percent receiving a placebo.

To many researchers the vaccines seem to be a potential answer to many of society's major ills; in the United States, there are 50 million cigarette smokers, 5 million drug addicts, 60 million obese adults and 9 million overweight young people between 6 and 19.

Most have one thing in common: They'd like to quit but can't. Nearly seven of 10 smokers, for instance, say they want to stop, but 80 to 90 percent of those who try to quit resume smoking within a year. The relapse problem is even worse for cocaine addicts.

"There is a great deal of promise for the nicotine vaccine not only as a smoking-cessation tool but also potentially as a relapse-prevention tool," said Dorothy Hatsukami, director of the Transdisciplinary Tobacco Use Research Center at the University of Minnesota Cancer Center.

"For those who have achieved abstinence and don't want to slip into relapse, being injected by the vaccine might be a good tool," said Hatsukami, whose preliminary data showed that in a small group of smokers the nicotine vaccine enabled 38 percent to remain abstinent for 30 days compared with 9 percent on a placebo.

The goal is getting people to give up cigarettes for a year. "If you can get someone past 12 months with being smoke-free, there's a 70 to 75 percent chance that that person will remain smoke-free," said Nabi official Thomas Rathjen.

Unlike most older vaccines, which tend to confer permanent immunity, the new breed of vaccines is reversible, providing immunity against nicotine, cocaine or ghrelin for one to three months before booster shots are needed. So far, none of the lifestyle vaccines has produced side effects other than some flulike symptoms and soreness at the injection site.

"These vaccines are not going to be a panacea for treating everything," said Kim Janda, of the Scripps Research Institute, a pioneer in developing vaccines for addiction and obesity.

"I believe they can be helpful. When people are undergoing abstinence for drugs of abuse and they have weak moments, if you have a vaccine in place it can assist them so they don't spiral down to ground zero."