New nicotine vaccine gives more effective immune response14 January 2015 A team at The Scripps Research Institute (TSRI) has designed a nicotine vaccine that elicits an effective immune response by using the 'left-handed' version of a molecule of a nicotine derivative. To prompt an immune response the scientists attached 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. Though 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. “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. An earlier version of the vaccine failed in clinical trials a few years ago and only worked in 30% of patients. The problem with the previous nicotine vaccine was that it did not single out the most common chemical form of nicotine for attack. Nicotine has two molecular forms that look like mirror images of each other — one is called right-handed version and the other left-handed version. Even though 99% of the nicotine found in tobacco is the left-handed version, the previous vaccine elicited antibodies against both. 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. Janda said considering molecule handedness is also 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,” Janda said. Reference Janda K et al. Conjugate Vaccine Using Enantiopure Hapten Imparts Superior Nicotine-Binding Capacity. Journal of Medicinal Chemistry. http://pubs.acs.org/doi/abs/10.1021/jm501625j |
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