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A Better Vaccine to Help Smokers Quit?

February 2015

Smoking is the leading cause of eight types of cancer, including lung cancer and fast-moving pancreatic cancer, according to the National Cancer Institute. A vaccine that can block nicotine from entering the brain could help people trying to quit smoking from relapsing; however, a past attempt at designing a vaccine only proved successful in 30% of patients.

Kim Janda is the Ely R. Callaway Jr. Professor of Chemistry and member of the Skaggs Institute for Chemical Biology at The Scripps Research Institute.

Now, a team of scientists at The Scripps Research Institute (TSRI) has designed a new, more effective nicotine vaccine that could help smokers quit for good. It also proves that the structure of molecules used in such vaccines is critical.

“This study provides new hope that one could make a nicotine vaccine that succeeds in clinical trials,” said Kim Janda, the Ely R. Callaway Jr. Professor of Chemistry and member of the Skaggs Institute for Chemical Biology at TSRI.

Nicotine vaccines train the body to see nicotine as a foreign invader. To prompt this immune response, scientists have tried attaching nicotine derivatives called haptens to a larger carrier protein used in other approved vaccines.

The body reacts to the vaccine by creating antibodies to bind specifically to nicotine molecules. When a person later uses tobacco, the anti-nicotine antibodies stop the nicotine molecules from entering the central nervous system and reaching the brain.

Although a vaccine wouldn't be a silver bullet (there would still be withdrawal symptoms), a person may be less motivated to relapse because the brain's reward system could no longer react to nicotine.

The problem with the previous nicotine vaccine was that it did not single out the most common form of nicotine for attack. Nicotine has two forms that look like mirror images of each other – one is a “right-handed” version and one is a “left-handed” version. Even though 99% of the nicotine found in tobacco is the left-handed version, the previous vaccine elicited antibodies against both. Dr. Janda believes that was a waste of immune response. “This is a case where something very simple was overlooked,” he said.

In the new study, the researchers elicited a more robust antibody response by creating a vaccine from only left-handed nicotine haptens. To do this, they prepared haptens as a 50-50 mixture and as pure right-handed or pure left-handed versions of nicotine, so they could use the two versions together or separately.

They tested both versions and the 50-50 mix in rat models, injecting the rats three times over 42 days. This series of “booster” shots gave the animals' immune systems a chance to create an effective number of antibodies to respond to nicotine.

The researchers analyzed blood from the three experimental groups and found that the left-handed hapten elicited a much more effective immune response. Compared with the right-handed hapten vaccine, the left-handed hapten vaccine prompted the body to create four times as many antibodies against left-handed nicotine molecules. The 50-50 mix was only 60% as effective as the pure left-handed version.

“This shows that future vaccines should target that left-handed version,” said Jonathan Lockner, research associate in the Janda lab and first author of the new paper. “There might even be more effective haptens out there.”

The researchers believe purifying nicotine hapten mixtures is an important and practical step in creating future nicotine vaccines. They also believe that molecule handed-ness is critical for developing vaccines against other drugs of abuse, such as cocaine and heroin. “This is just one area where we are looking outside the box to try to treat addiction,” Dr. Janda said.

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