The Anti-Smoking Vaccine

By Jeffrey Helm, The Tyee. Posted September 30, 2006.

Someday, along with jabs against mumps and measles, kids could get vaccinated against nicotine, cocaine and heroin.

Vaccines for cocaine and nicotine have already been tested in humans. Nicotine vaccines, in particular, are getting a lot of attention.

This summer a recruitment campaign got under way across the United States for clinical trials of NicVAX, a nicotine vaccine. Nabi Pharmaceuticals says it is developing NicVAX in order to help "billions worldwide who are addicted to smoking tobacco products or are at risk of becoming addicted."

But vaccines against a drug are different from normal vaccines against disease-causing viruses and bacteria. Normal vaccines prevent disease from taking hold. That is not the focus of drug vaccines like NicVAX.

"The target for [drug] vaccines right now is treatment or relapse prevention," says Dr. Paul Pentel from the University of Minnesota, one of the leading researchers in nicotine vaccine development. "It's simply way to early to know if vaccines would be appropriate for [addiction] prevention."

Even so, that won't prevent the off-label use of a product like NicVAX. Off-label use is when doctors prescribe a drug for something other than what it was originally meant for, and for some drugs, off-label use accounts for the bulk of their sales.

Whether the purpose is treatment or prevention, a vaccine made against a drug would soak up the drug and prevent it from working. Even if a smoker who was trying to quit slipped and lit up, the cigarette would just tar up their lungs a little more. No buzz, just stinky hot smoke. An effective nicotine vaccine would force you to quit cold turkey whether you wanted to or not. Which is both a strength and a potential problem of such treatments.

How an anti-drug vaccine works

Vaccines work by getting your body to produce antibodies, which are molecules designed to bind. They are tailor-made to latch onto and immobilize anything foreign that catches the attention of your immune system. Antibodies are also very specific. An antibody against a virus, like polio, won't work against anything else.

Normally the body does not make antibodies that target drugs because drug molecules are too small. They need to be small so that they can move easily from the blood to where they work in the brain.

In order for the immune system to make antibodies against a drug, a piece of the drug molecule is joined to a larger protein that the immune system will pay attention to. Then the body will start making antibodies that will grapple onto the drug.

With a standard immune response, other cells chew up bound antibodies, and whatever they are hanging onto. This does not happen with vaccines for drugs; the antibodies just stay latched to the drug molecules. But now the drug molecule is much bigger since it has an antibody stuck to it. So big, that the bound drug can't get into the brain to do any harm. Neither can it interact with anything else in the body.

A few party crashers help withdrawal

The intended use of NicVAX, and other drug vaccines in development, is to help people quit and stay clean.

In a small preliminary study, 40 per cent of smokers on NicVAX quit, as compared to a 9 per cent quit rate of those on a placebo (fake drug). "That differential was the largest differential of any smoking cessation product ever tested," Tom Rathjen, vice-president of investor relations for Nabi Biopharmaceuticals, said.

Great results, even when some of the nicotine is getting to the brain.

Shutting out the drug completely from the brain was the initial idea, but the antibodies made from NicVAX let a little nicotine through -- which actually isn't so bad. The small amount of nicotine that gets through lessens withdrawal symptoms, and for reasons that are not entirely clear, the entry of unbound nicotine into the brain is also slowed. This slowing of nicotine entry also reduces its addictive strength.

"The reinforcing properties of nicotine are greatest in the first few seconds or minutes after a puff of a cigarette," Pentel said. "If it's possible to slow the entry of nicotine into the brain, this could potentially reduce its subjective and its addictive effects."

But I don't like needles

Physicians have concerns with drug vaccines, like NicVAX, beyond possible allergic reactions that come with any vaccine. With a vaccine against a drug, whenever the drug is taken, bunches of antibody-drug formations fill the blood stream. When more than one antibody binds to a drug, the resulting clump, called an antigen-antibody complex, can cause problems. Dr. David Marsh, who is the head of Addiction Services for Vancouver Coastal Health, expressed concern that drug vaccine studies have not always looked at antigen-antibody complex effects because they are difficult to study. "I'm not sure if the trials to date have addressed the potential risks of that, like glomerular nephritis (kidney problems), or other problems that antigen-antibody complexes are known to cause." Although antigen-antibody complexes may still be a concern for other drug vaccines in development, for NicVAX it doesn't appear to be a problem. The antibodies produced with NicVAX bind nicotine one-to-one, so no antigen-antibody complexes would be formed that could damage the kidney. Another concern, and potential benefit, would be the longevity of the treatment. Some traditional vaccines against disease can give you immunity for life -- immunity that you cannot reverse. A lifelong effect is much more economical than a regime of pills, but, as a general rule, non-reversible treatments make doctors nervous. If something goes wrong, you cannot stop the treatment. Although NicVAX does last a long time, the effects are not lifelong, so the treatment should be reversible in time. Preliminary studies have shown that a treatment of NicVAX lasts for 12-18 months.

Jeffrey Helm, a former neuroscientist, is writing about science and addiction issues for The Tyee this summer. Read his series here.

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