Dr. Thomas Kosten, a professor and the Jay H. Waggoner Endowed Chair in the Menninger Department of Psychiatry and Behavioral Sciences at Baylor College of Medicine in Houston, Texas, discusses the concept and current status of antidrug vaccines to treat substance use and addiction.
NIDA Notes: What is the basic idea behind antidrug vaccines?
In this podcast, Dr. Thomas Kosten discusses antidrug vaccines’ potential for facilitating substance use treatment and prevention.Dr. Kosten: The fundamental approach underlying an antidrug vaccine is the same as for a vaccine against a pathogenic virus or bacterium: You inject a person with an antigen, which is an agent that will stimulate production of antibodies.
In an antidrug vaccine, the antigen consists of the target drug linked to a large carrier protein such as tetanus toxoid or cholera toxin. The carrier protein is necessary because the drug molecule by itself is too small to stimulate antibody production. The carrier protein triggers production of antibodies that target the drug as well. If the vaccinated person subsequently takes the drug, these antibodies bind it and prevent it from entering the brain and other organs. The person doesn’t get high from the drug and is shielded from its other harmful effects. [Watch an animation depicting how antidrug vaccines work.]
NN: What happens to the drug after the antibody binds it?
Dr. Kosten: That depends on the particular drug. In the case of cocaine, an enzyme is naturally present in the blood that breaks down the drug. The enzyme, called cholinesterase, increases the cocaine vaccine’s effectiveness, because in addition to inactivating the drug, it also frees up antibody to bind more drug.
For other drugs, such as methamphetamine and nicotine, the drug is metabolized when it passes through the liver. That process also frees up antibody, but it doesn’t assist those vaccines’ efficiency as much as cholinesterase does the cocaine vaccine’s. The reason is that it only happens in the liver, instead of throughout the bloodstream, and it takes time for the drug-antibody complex to reach the liver.
NN: Would a single treatment with an antidrug vaccine be enough?
Dr. Kosten: No. Booster shots will be required.
For an antidrug vaccine to be effective, the antibody response to it must be substantially greater than that typically produced by an infectious-disease vaccine. The antidrug vaccines we are developing stimulate production of 100 to 1,000 times more antibody than is produced with a typical vaccine against an infectious disease. After the initial vaccination, antibody levels rise and stay very high for 2 to 3 months. Each booster will push the antibody levels back up for another 2 to 3 months. The antibody levels may stay up for a longer time after each booster shot, as occurs with the tetanus vaccine. But they certainly will not last for years and will drop off to undetectable levels within 9 to 12 months.
NN: What are the potential risks of the antidrug vaccination?
Dr. Kosten: The primary risk is that a user takes a large amount of the drug to try to override the vaccine. The antibodies act like a sponge that keeps the drug in the blood stream and prevents it from rapidly entering the brain and causing the euphoria the user seeks. But a full sponge is leaky, and so at high doses, some amounts of the drug are regularly coming off the antibodies. The drug enters the brain and other organs, albeit slowly, and even though the person doesn’t get high, it may produce harmful effects. In the case of stimulants, for example, these might include anxiety, paranoia, or even cardiovascular events. In fact, these toxic effects may be worsened because the organs are being exposed to higher amounts of the drug. This means that we have to think very carefully about unanticipated negative consequences of the vaccines and use them only in people who are determined to stay abstinent.
NN: Do the vaccines themselves have any adverse physiological effects?
Dr. Kosten: We have been using these vaccines since 1996, and we’ve had very few adverse events and have not observed any serious adverse events. The antidrug vaccines are based on vaccines that have been tested for more than 50 years and have been given to millions of people.
NN: Have any of the antidrug vaccines been approved for clinical use yet?
Dr. Kosten: All of the antidrug vaccines are still in development or in various clinical trial phases and not yet available for use outside of research. However, the antidrug vaccine field is a very active area. It’s very satisfying after working in it for 20 years to see the enthusiasm that it generates.
NN: What did you find in your most recent clinical trials?
Dr. Kosten: We completed a small, single-site placebo-controlled clinical trial in which we found that the people who got the vaccine used cocaine less often than those who did not receive the vaccine. Slightly above one-third of the people had higher antibody levels of about 40 micrograms per milliliter, and these patients substantially reduced their cocaine use.
We repeated the study at a national level with six sites with a slightly reformulated vaccine, and we found that almost two-thirds of the patients attained the higher antibody levels. In this study, the patients were actively using cocaine. Many of the patients overrode the blockade by taking more of the drug. But three-fold more people with the higher antibody levels were able to get 2 or more weeks of abstinence than those who were treated with the placebo or who had the lower antibody levels. The trial also confirmed that antidrug vaccine studies should enroll people who are very motivated and able to stop using cocaine.
NN: What are your plans for the future?
Dr. Kosten: We’re excited about the second-generation anti-cocaine vaccines that we’ve developed. These vaccines have an adjuvant, which is either a protein or a lipid molecule that markedly increases the antibody production after vaccination. With these adjuvants, we can stimulate higher levels of antibodies in more people. We have adjuvants not only for the nicotine vaccines, but also our cocaine and methamphetamine vaccines.
We also want to make the enzyme that breaks down cocaine—cholinesterase—much more active. Our collaborators have developed enzymes from bacteria that have 1,000 to 10,000 times the activity of the cholinesterase in people. We found that even a poorly functioning vaccine in combination with these high-activity enzymes completely blocks the effects of cocaine. These new ideas for combining biological interventions may lead to vaccines that in the case of cocaine could produce a sustained blockade of the drug’s action.