Fentanyl vaccine: Could it be a turning point in the opioid pandemic?

By Samar Mahmoud, PhD | Medically reviewed by Amanda Zeglis, DO, MBA
Published March 17, 2023

Key Takeaways

  • Researchers have developed a fentanyl vaccine, tested in rodents, that generates significant anti-fentanyl antibodies that bind to fentanyl and prevent it from entering the brain. 

  • To date, the vaccine has not been tested in humans, but it has the potential to be a game-changer in the opioid epidemic. 

  • The risk of adverse events in humans is low, as two components of the vaccine are both utilized in other existing vaccines approved for use in humans.

Researchers at the University of Houston have developed a fentanyl vaccine that blocks the synthetic opioid from entering the brain. Not yet tested on humans yet, if effective, the vaccine has the potential to be a major breakthrough in the opioid epidemic. 

The opioid crisis 

The number of opioid-related overdose deaths has increased dramatically since 1999, with levels 5 times higher in 2020 than in 1999, according to the CDC. [] 

Over those years, more than 564,000 people have died from an opioid overdose. This includes both prescription and illegal opioids. 

The CDC reports that the increase in opioid overdose deaths has occurred in three waves. The first wave coincided with the increase in opioid prescriptions beginning in the 1990s. In 2010, the second wave began, with a surge in overdose deaths related to heroin use.

Synthetic opioids, such as fentanyl, ushered in the third wave in 2013. Back in 2010, only 14.3% of opioid-related deaths were due to fentanyl use. But by 2017, this proportion was 59%, making fentanyl and other synthetic opioids the most common drugs involved in overdose deaths in the United States.[] 

Current treatment challenges 

Current treatments for opioid use disorder include methadone, buprenorphine, and naltrexone. The efficacy of these medications depends on many factors, including the kind of opioid, the formulation of the drug, patient compliance, and access to the medications. 

Fentanyl overdose is treated with naloxone, a short-acting antagonist that works by binding to opioid receptors and reversing the effects of opioid drugs. 

One of the drawbacks associated with the use of naloxone is the need for multiple doses in order to counteract the potentially fatal effects associated with fentanyl use. 

Researchers at the University of Houston have proposed that, to overcome the treatment challenges, there is a need for immunotherapies capable of blocking fentanyl from entering the brain.[] Their preclinical studies provide evidence that a fentanyl vaccine is possible.

A potential fentanyl vaccine? 

The University of Houston investigators studied an anti-fentanyl conjugate vaccine composed of a fentanyl-like compound that is linked to CRM197, a carrier protein present in various FDA-approved conjugate vaccines. The fentanyl-CRM conjugate is then combined with dmLT, an adjuvant that is found in other vaccines that have been assessed in multiple human clinical trials. 

In their previous studies in mice, the research team had discovered that administration of the fentanyl vaccine produced a significant amount of anti-fentanyl antibodies, blocking the analgesic effects of fentanyl.

In their studies in rats, published in Pharmaceutics, they found that the conjugate vaccine has the following effects: 

  • Produces long-lasting anti-fentanyl antibodies that bind to fentanyl and not other opioids

  • Blocks fentanyl-induced nociception in pain-response tests 

  • Decreases brain levels of fentanyl following administration of fentanyl 20 weeks after the initial vaccination 

  • Protects against fentanyl-induced decreases in heart rate, activity levels, and oxygen saturation

  • Blocks the rate-disrupting effects of fentanyl, but not morphine, during schedule-controlled responding, a pharmacological behavioral test to evaluate drugs


The preclinical results presented in the study have significant implications for the treatment of opioid use disorder and overdose in humans, as discussed in a press release announcing the study.[] Because CRM and dmLT are both utilized in existing vaccines approved for use, the risk of adverse events to humans is likely low. 

In the press release, Colin Haile, MD, PhD, research associate professor of psychology at the University of Houston and the study’s lead author, expressed his opinion on the implications.

"We believe these findings could have a significant impact on a very serious problem plaguing society for years—opioid misuse."

Colin Haile, MD, PhD, study author

"Our vaccine is able to generate anti-fentanyl antibodies that bind to the consumed fentanyl and prevent it from entering the brain, allowing it to be eliminated out of the body via the kidneys," said Dr. Haile. "Thus, the individual will not feel the euphoric effects and can ‘get back on the wagon’ to sobriety.”  

What this means for you 

A fentanyl vaccine has been developed and tested in rodent models. If successful in humans, this vaccine could help individuals trying to recover from opioid use disorder, as it prevents fentanyl from entering the brain and eliciting euphoric effects. 

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