A Vaccine Against Fentanyl!

A novel approach to treating opioid addiction is in development.

Reviewed by Hara Estroff Marano

Key points

• Treatment of substance use disorders (SUDs) is improving but marked by relapse and overdose.
• Animal studies have yielded major advances in vaccine technology for SUD treatment over the past 50 years.
• An anti-fentanyl vaccine is promising and could end the fentanyl overdose and death epidemic.
• Not an overnight success, 36 years of work has gone into an anti-fentanyl vaccine.

What if someday there were a way to prevent death from an overdose of fentanyl—whether the drug was taken purposely or accidentally (as when fentanyl is included in other drugs, and no one told the drug user)? It’s not ready for prime time yet, but a vaccine against fentanyl is under active development and expected to be tested on humans in 2025.

Thomas Kosten, M.D., Waggoner Professor of Psychiatry, Pharmacology, Neuroscience, Immunology at Baylor College of Medicine in Houston, Texas. is the creator of the vaccine. Animal studies have been completed, and the vaccine has been transferred to the control of a new start-up, Ovax. Human studies are likely to get underway in 2025. Kosten and his team developed the anti-fentanyl agent based on more than 36 years of innovative work in substance use disorder-specific vaccine discovery and development.

The anti-fentanyl vaccine is extremely important. Even though the number of fentanyl overdoses is down somewhat from past years’ highs, 74,702 people died in 2023 alone due to fentanyl. Far too many people of all ages still overdose and die from fentanyl throughout the United States.

The surge in fentanyl overdoses regenerated interest in vaccine immunotherapy, which, despite an optimistic start with animal models over the past 50 years, has yielded disappointing results in human clinical trials. Vaccines against nicotine, stimulants (cocaine and methamphetamine), and heroin, have all stalled.

While the FDA has approved three treatment medications for opioid use disorder—naltrexone, buprenorphine, and methadone—all fail to prevent fentanyl overdoses. In contrast, it is hoped a future fentanyl vaccine may be a major addition to the arsenal of weapons against overdose, addiction, and death.

“We’re enthusiastic about broad vaccination of abusers because illicit fentanyl is being added to stimulants like Adderall and counterfeit prescription opiates like oxycontin, and we don’t have anything else that blocks fentanyl,” Kosten says.

When most people think of vaccines, they view them as disease preventives, blocking infections such as polio and rubella, and. more recently, COVID-19, all designed to protect against a specific disease. Fentanyl, however, is nothing like a virus, and the immune system normally ignores it. But by linking fentanyl-like molecules to other proteins, scientists can force the immune system to recognize opioids as foreign and generate antibodies to fight them. In experiments at Baylor, Kosten's vaccine successfully blocked fentanyl-induced respiratory depression and lethal overdose.

Unlike current treatments for overdose, such as naloxone or Nalmefene, the fentanyl vaccine could offer lasting protection against the drug. Although it cannot work immediately, the vaccine takes effect in about a month. Thus, if a person overdosed and recovered in March, was vaccinated, and then took fentanyl again in July, she will not overdose again because the vaccine will block the drug. Fentanyl vaccines may also be used as part of treatment for individuals in recovery, combined with other treatments like methadone or buprenorphine.

Kosten and his team developed their anti-fentanyl vaccine based on years of Kosten’s work in vaccine discovery and development. The idea of treating drug addiction with a vaccine is exciting but not new. Research dating back to the 1970s at the University of Chicago showed that a vaccine could stop monkeys from self-administering heroin; in the 1980s, researchers tried to develop vaccines for cocaine and nicotine. Sadly, they did not succeed

Having handed off his vaccine to private developers, Kosten has returned to his work on vaccines targeting stimulants such as cocaine and methamphetamine, although many years of research lie ahead.

Who Would Take the Fentanyl Vaccine?

One market for the future fentanyl vaccine is patients treated for substance use disorders. A vaccine could be given after the evaluation phase of residential treatment for speedballing or fentanyl addiction. Similarly, it could be given to patients being treated with buprenorphine or methadone for an opioid use disorder and to patients who feel their disease is in remission. “We’re not vaccinating people forever,” Kosten says. “It’s effective for about six months and then requires a booster of the vaccine for six more months of efficacy.”

It might even be given prophylactically to first responders, such as police and emergency medical responders. It is assumed that such individuals would not abuse fentanyl, but even an accidental contact with the drug has been shown to cause harm to first responders.

However, most of those to be immunized against fentanyl would be people addicted to fentanyl or other drug users who might accidentally ingest fentanyl, often added as a filler to drugs such as methamphetamine, cocaine, MDMA (ecstasy), and others.

Importantly, vaccines do not preclude an individual from receiving pain management if they develop a severely painful medical problem. For example, a person vaccinated against fentanyl who develops agonizing pain from appendicitis or a kidney stone can be given an opioid other than the one vaccinated against. Says Dr. Kosten, “Every other non-fentanyl opioid would be effective as an analgesic. Only fentanyl is blocked by the vaccine.”

Combining Existing Therapies to Treat Addiction

Vaccines are being explored as complementary to existing treatments like medication-assisted therapy, residential treatment, and behavioral therapies. While vaccines for opioid use disorder and other addictions are still experimental, they represent a promising frontier in addiction treatment.

Critical advancements may occur in the next few years as more novel therapies enter clinical trials, researchers individualize treatment, and researchers develop new algorithms for treatment recidivism.