Researchers Develop New Type of Vaccine Against Nicotine
By Jason Socrates
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
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
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."