The obesity shot
Vaccinating against one of the body’s own hormones seems counterintuitive, or even dangerous. But to ease the obesity epidemic, a vaccine that targets ghrelin—a gastrointestinal hormone that appears to stimulate appetite—could be well worth the risk. Here, too, the strategy is to micromanage how certain molecules behave in the body.
“When you diet, the body responds as if it were starving and produces ghrelin to slow down fat metabolism and stimulate eating,” explains Eric Zorrilla, a neuroscientist specializing in eating disorders at the Scripps Research Institute in La Jolla, California. Zorrilla’s experimental antiobesity vaccine consists of ghrelin molecules chemically linked to hemocyanin, a protein extracted from the keyhole limpet marine snail. Hemocyanin is known to provoke a powerful immune response in humans. In theory, the response to a vaccine combining ghrelin and hemocyanin should clear ghrelin from the bloodstream.
After trying several biochemical configurations, Zorrilla and colleague Kim Janda hit on one in 2006 that caused immunized mice to lose weight. There are potential dangers to immunizing against the body’s own chemicals, though. In particular, the researchers must ensure that their vaccine does not result in an autoimmune response to cells that produce ghrelin, which could trigger severe swelling and inflammation. “We didn’t see evidence of that in the animal studies, but it’s a concern,” Janda says. He and Zorrilla continue to refine the vaccine in preparation for human trials.
Potential patients: Nearly 75 million adults are classified as obese in the United States.
The addiction shot
Efforts to produce anti-addiction vaccines began in the 1970s, but those currently in clinical trials trace back to newer research from the mid-1990s, when Barbara Fox, then an immunologist at ImmuLogic Pharmaceutical Corporation, helped develop a cocaine vaccine. The hurdle, she explains, was to get the immune system to register and attack the small, relatively uncomplicated cocaine molecule rather than the complex biological proteins typically found on microbes.
“We had to couple the cocaine to a carrier protein,” Fox explains. “We needed a longer molecule that the immune system could recognize as foreign and dangerous.” Eventually Fox and her colleagues attached a cocaine molecule to one piece of the deadly toxin produced by cholera bacteria. “This molecule itself isn’t toxic,” Fox says. “But it’s the part that generates the strongest response from the immune system.”
In lab animals the vaccine prompted the immune system to produce antibodies custom-tailored to attach to cocaine molecules. Once bonded, the antibodies make the cocaine molecules too large to slip through the tight blood-brain barrier. As a result, the chemical cannot deliver its pleasurably addictive effects to the brain.
Fox’s vaccine has been sustained and improved by psychiatrist Thomas Kosten at Baylor College of Medicine in Houston. In 2009 Kosten reported the results of a clinical trial with 115 cocaine addicts, half of whom received the vaccine. The others received dummy shots. The vaccine produced a strong antibody response in 38 percent of those who received it. These patients were cocaine-free at 45 percent of their follow-up exams two to four months after receiving the vaccine.
What’s more, the urine tests used to verify abstinence revealed that several users had tried to thwart the vaccine by overdosing. “Some urine samples showed cocaine levels over a million,” measured in nanograms per milliliter, Kosten says. “I’ve never seen any living person with over 100,000.” Yet no one was dying of heart attack or stroke, as would be expected if a high level of cocaine reached the heart or brain. In fact, the participants reported that they were not feeling much of anything. The vaccine is currently in a national clinical trial expected to end within the year.
Kosten is also researching vaccines for methamphetamines and opiates, which are among several anti-addiction shots that have the keen interest of the National Institute on Drug Abuse, says NIDA director Nora Volkow, a research psychiatrist who has used brain imaging to investigate the addictive properties of drugs. NicVAX, an antismoking vaccine that recently received $10 million in funding from NIDA, is in large clinical trials under the auspices of its maker, Nabi Biopharmaceuticals. The vaccine generates antibodies to nicotine by linking the addictive molecule to an inactivated bacterial toxin. As with the cocaine vaccine, the resulting antibodies do not clear nicotine from the blood so much as stick to it, creating a chemical complex too large to migrate into the brain.
Volkow was initially skeptical about the possibility of a nicotine vaccine. “I thought people would simply overcompensate by smoking more cigarettes,” she says. But in a pilot study conducted on heavy smokers, 24 percent of those who received the NicVAX vaccine were smoke free for the last two months of the six-month study—double the quit rate of those who received placebo shots. Among those who developed antibodies to nicotine but were not able to abstain from smoking, the number of cigarettes they smoked dropped significantly.
It is too soon to know how long these vaccines will last and whether they will prevent addicts from switching to other drugs. But NIDA is embracing the approach and is now researching a vaccine against heroin, the use of which is a vector for HIV transmission in many countries. Volkow has moved past her doubts about addiction vaccines. “That was before I saw the results of early trials,” she says. “Now I see how vaccine technology can be used against a host of public health issues.”
Potential patients: 46 million Americans smoke cigarettes; an estimated 1.6 million used cocaine in 2009.
Jessica Snyder Sachs is the author of
Good Germs, Bad Germs: Health and Survival
in a Bacterial World.