New nicotine vaccine gives more effective immune response
14 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
“This is just one area where we are looking outside the box to
try to treat addiction,” Janda said.
Janda K et al. Conjugate Vaccine Using Enantiopure Hapten
Imparts Superior Nicotine-Binding Capacity. Journal of