Researchers Develop New Type of Vaccine Against Nicotine Addiction

By Jason Socrates Bardi

Scientists at The Scripps Research Institute (TSRI) have designed a new way to make vaccines against drugs of abuse that could become a valuable tool for treating addiction by helping the body clear the drug from the bloodstream.

The latest vaccine they created using this approach induces the body to clear nicotine.

"These new vaccines greatly suppress the reinforcing aspects of the drug," says principal investigator Kim D. Janda. "Blocking it before it gets to the brain—thatís the key."

The structure and design of the nicotine vaccine are described in an article that will be published in an upcoming issue of the Journal of the American Chemical Society. Research Associate Michael M. Meijler, who is the article's lead author, synthesized this vaccine under the guidance of Janda, who holds the Ely R. Callaway, Jr. Chair in Chemistry and is an investigator in The Skaggs Institute for Chemical Biology at TSRI.

Having shown the vaccine's effectiveness in laboratory models, Meijler and Janda have now reformulated the vaccine for investigation for use in human trials. Eventually, this sort of vaccine would be given to people undergoing smoking cessation programs to aid in their recovery.

Many believe that people continue to smoke because tobacco contains nicotine, which is an addictive chemical. Many smoking cessation strategies, in fact, provide cigarette addicts with nicotine from sources other than tobacco—such as patches or gum.

Janda and his laboratory, however, have taken an "immunopharmacotherapy" approach. That is, they have designed a drug that stimulates the immune system to clear the nicotine from the system. They based this work on previous successes Janda had in developing a vaccine for another addictive drug—cocaine—which is currently in clinical trials.

The new idea that they have developed is to take a chemical that resembles nicotine and use it to induce an active immune response. In this immune response, the body produces antibodies against nicotine that can neutralize it in the bloodstream. If a smoker later smokes a cigarette, the antibodies will clear the nicotine from the system before it reaches the brain.

Developing a nicotine vaccine proved difficult. At first, Janda and his colleagues were not able to induce an effective immune response as they had previously with cocaine. Then Janda and Meijler realized that the difference could be that cocaine is a relatively inflexible molecule where nicotine has a flexible axis that allows it to adopt multiple shapes.

Janda and Meijler had been designing a vaccine that was equally flexible, and so they decided to make one that was rigid and resembled only one form of nicotine.

"These [induced] antibodies make a much more focused immune response," says Meijler. In fact, he adds, the vaccine is better because it induced a larger antibody response and the antibodies themselves bound more tightly (with higher affinity) to the nicotine.

Furthermore, adds Janda, "This could be a general method for vaccine development for drugs of abuse—period."



Professor Kim Janda and his laboratory have designed a drug that stimulates the immune system to clear nicotine from the system. A figure illustrates the improved immune response.