A Weak Smoker’s Vaccine Might Be Worse Than None

New PET scans show wide responses to antibodies.

One of the brightest hopes of addiction science has been the idea of a vaccine—an antibody that would scavenge for drug molecules, bind to them, and make it impossible for them to cross the blood-brain barrier and go to work. But there are dozens of good reasons why this seemingly straightforward approach to medical treatment of addiction is devilishly difficult to perform in practice.

Last January, health care company Novartis threw in the towel on NicVax, a nicotine vaccine that failed to beat placebos in Phase III clinical trials for the FDA. And back in 2010, a report in the Archives of General Psychiatry demonstrated that a vaccine intended for cocaine addicts only generated sufficient antibodies to dull the effects of the cocaine in 38 percent of the test subjects. Moreover, it proved possible to overcome immunization by upping the cocaine dose, which sounded like an invitation to overdose.

And now, neuroscientists at the Society of Nuclear Medicine and Molecular Imaging annual meeting have presented a new study, the conclusions of which might help researchers understand why the vaccine results have been so mixed. The research “represents one of the first human studies of its kind using molecular imaging to test an investigational anti-nicotine immunization,” lead author Alexey Mukhin, professor of psychiatry and behavioral science at Duke University Medical Center, said in a prepared statement.


Subjects underwent two PET brain scan as they smoked nicotine labeled with radioactive C-11, one before the vaccine was administered, and one after. Ten subjects who developed “high-affinity antibodies” after vaccination showed a slight decrease in nicotine accumulation in the brain, as judged by the scans. However, another group of ten subjects, who showed “intermediate serum nicotine binding capacity and low affinity of antibodies” actually showed an increase in brain nicotine levels. What the PET scans showed was that “strong nicotine-antibody binding, which means high affinity, was associated with a decrease in brain nicotine accumulation. When binding was not strong, an increase in brain accumulation was observed.”

If the bond that holds the antibodies to the nicotine molecules is weak, the bond can break during passage through the blood-brain barrier, potentially allowing excess nicotine to flood in. This result, said Mukhin, tell us “we should care about not only the amount of antibody, but the quality of the antibody. We don’t want to have low-affinity antibodies because that can negate the anti-nicotine effects of the vaccination.”

Back to the drawing board? Not entirely. Another of the study authors, Yantao Zuo of Duke University Medical Center, said that “with reports of new generations of the vaccines showing potentially much higher potencies in animal studies, we are hopeful that our current findings and methodology in human research will facilitate understanding of how these work in smokers.”

Photo Credit:http://www.medgadget.com

Vaccinating Against Vices

Developing a pill or a vaccine for a specific drug addiction has long been one of the tantalizing potential rewards of addiction research. Now a company in Florida has garnered national attention, a spate of clinical trails, and a positive response from the National Institute on Drug Abuse (NIDA) with a compound called NicVAX, aimed at nicotine addiction. In addition, Celtic Pharma in Bermuda is working on a similar product for cocaine addiction.

The idea of vaccinating for addictions is not new. If you want the body to recognize a heroin molecule as a foe rather than a friend, one strategy is to attach heroin molecules to a foreign body--commonly a protein which the body ordinarily rejects--in order to switch on the body’s immune responses against the invader. The idea of a vaccine for cocaine, for example, is that the body’s immune system will crank out antibodies to the cocaine vaccination, preventing the user from getting high. A strong advantage to this approach, say NIDA researchers, is that the vaccinated compound does not enter the brain and therefore is free of neurological side effects.

Preliminary research at the University of Minnesota showed that a dose of vaccine plus booster shots markedly reduce the amount of nicotine that reaches the brain. Animal studies have shown the same effect. NicVAX, from Nabi Biopharmaceuticals, consists of nicotine molecules attached to a protein found in a species of infectious bacteria. When smokers light up, antibodies attack the protein-laden nicotine molecules, which, further encumbered by these antibodies, can no longer fit through the blood-brain barrier and allow the user to enjoy his smoke.

That, at least, is the idea. It is a difficult and expensive proposition, the closest thing to a miracle drug for addiction, but it does not specifically attack drug craving in addicted users. The idea of vaccination is that, once a drug user cannot get high on his or her drug of choice, the user will lose interest in the drug.

This assertion is somewhat speculative, in that users of the classic negative reinforcer, Antabuse, have found ways to circumvent its effects--primarily by not taking it. There remain a wealth of questions related to the effects of long-lasting antibodies. And it is sometimes possible to “swamp” the vaccine by ingesting four or five times as much cocaine or nicotine as usual.

Drugs that substantially reduce the addict’s craving may yet prove to be a more fruitful avenue of investigation. While several anti-craving medications have been approved for use by the Food and Drug Administraton (FDA), no vaccines have made it onto the approved least yet.

For more on pharmaceutical approaches to fighting drug addiction, see my website at http://www.dirkhanson.org