CAN VACCINES CURE OUR BAD HABITS?

Researchers Aim Syringes At Smoking, Obesity, Drugs

Vaccines, the most potent medical weapon ever devised to vanquish
deadly germs, are now being called on to do something totally
different and culturally revolutionary--inoculate people against bad
habits like overeating, cigarette smoking and drug use.

Whether this new era of vaccine research can actually 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 under way in
Switzerland are expected later this year and company officials are
hopeful that the vaccine could be ready for use in a few years.

To tamp out deleterious behavior, the new vaccines employ the body's
natural 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.

"I'm trying to cut back because cigarettes don't taste so good
anymore," said James VanHall, a truck driver for the City of
Minneapolis who is participating in a trial of the anti-nicotine
vaccine at the University of Minnesota. Although he doesn't know if
the three shots he has received since June are the vaccine or a
placebo, VanHall says he can tell they are having an effect.

"Cigarettes pretty much tasted good all my life, but right now it
seems like I'm smoking a light cigarette or something," said VanHall,
50, who has been smoking since his early teens and would go through a
pack or a pack and a half a day. "There's hardly any flavor there.
I'm hoping the vaccine works because this is the worst thing I've
ever tried to quit in my life."

Several months into the study, VanHall stopped smoking altogether.
It's hard, he said, but he has less craving for cigarettes now than
when he tried to quit in the past.

In the case of the obesity vaccine, antibodies attach to the hunger
protein called 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 believe, is
that dieting causes large amounts of ghrelin to be produced as the
body seeks to stimulate eating, slow down the metabolism of fat and
promote fat retention. Ghrelin also may help explain the yo-yo
experience of millions of people who try to lose weight but end up
putting on more pounds.

"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, the animals 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, making them leaner.

Cytos also is 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, a biotech
company in Boca Raton, Fla., is expanding trials of NicVAX after a
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 U.S. there are 50 million
cigarette smokers, 5 million drug addicts, 60 million obese adults
and 9 million overweight youngsters between ages 6 and 19.

Most have one thing in common: They'd like to quit but can't. Nearly
7 out of 10 smokers, for instance, say they want to stop, but 80
percent 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 the hunger hormone ghrelin for one to three
months before booster shots are needed. None of the new 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."