Behind the Vaccine Against Fentanyl

Lead researcher Colin Haile speaks from the lab about the discovery that shields the brain against one of the world's deadliest drugs.

By Tyler Hicks

In September 2022, the Los Angeles Unified School District made an announcement that sent chills down Colin Haile’s spine. Narcan—an emergency medicine that can temporarily reverse the effects of opioids like fentanyl—will now be available in all K-12 schools, the district said. Fentanyl overdoses had become so common that the district was now, in its own words, facing a “community crisis” that required a dramatic response.

For Haile, an addictions researcher and UH research associate professor of psychology, the news was yet another confirmation that his current project is critical.

“Even before we started this work, roughly five or six years ago, there were signs that fentanyl use and overdose deaths were on the rise,” Haile says. “Now, it’s gotten to the point where fentanyl is taking tens of thousands of lives each year, and we’ve got to do something about this.”

And he is.

Haile is part of a UH research team that has spent the past five years developing a vaccine that, in tests thus far, has proven to block fentanyl from reaching the brain. This development is essential, since fentanyl’s ability to quickly reach the brain is the reason the drug is so addictive.

If the FDA approves the anti-fentanyl vaccine for mass use—and Haile is confident they will—it will be a historic breakthrough in the fight against a uniquely dangerous opioid. FDA approval would also mark the end of a challenging development process in which Haile and his team have relied on a blend of creativity, grit and in-depth science savvy.

“It’s been a long and difficult road,” Haile says, recapping his team’s work thus far. “But we’re optimistic about the road ahead.”

According to the National Institute on Drug Abuse, there were more than 106,000 drug overdose deaths in 2021. The majority involved synthetic opioids such as fentanyl, which took 70,601 lives.

Haile, who speaks in a calm, measured tone, has a scientist’s zeal for the practical and a natural aversion to exaggeration. Still, he is quick to point out just how dangerous fentanyl can be.

“Two grams can kill an individual, and a few grains of some of its derivatives can compromise someone,” he says. “One derivative, carfentanil, is used in veterinary medicine to anesthetize large animals like elephants.”

He pauses.

“And we’re talking about a drug that can be found on the streets, sometimes hidden in other illicit drugs.”

When people consume fentanyl, they’ll feel euphoric effects—and, often, respiratory depression. They’ll lose control of their diaphragm, and the walls of their chest freeze up, resulting in what’s called “wooden chest syndrome.”

This reaction is all because of the drug’s mad dash to the brain, which Haile's vaccine has been proven to prevent.

The innovation is a departure from typical vaccines. It’s best to rely on Haile’s explanation to understand how it works:

“In a prototypical vaccine, you’re vaccinated with a piece of bacteria or virus you want to be protected against,” the researcher says. “Your body recognizes it as foreign, then develops antibodies against that pathogen. What we’ve done here is [produced] a vaccine that [creates] antibodies against a chemical: fentanyl. We vaccinate, and the individual develops anti-fentanyl antibodies, which bind to the chemical and prevent it from getting to the brain, instead keeping it in the blood until it is eventually eliminated from the body.”

The vaccine completely blocks fentanyl’s effects for 5-6 months in trials with rats. It remains to be seen how enduring the antibodies are in humans.

Vaccinating against an opioid is a unique proposition; however, Haile has worked on developing other vaccines against substances associated with use disorders, including anti-cocaine and anti-methamphetamine vaccines. Even still, the team encountered several roadblocks during their multiyear journey.

At one point in their studies on mice and rats, Haile’s group noticed extremely low levels of antibodies in the test animals, despite fentanyl’s effects being fully blocked. They spent weeks searching for the answer, ultimately discovering that the problem lay with one reagent used in the detection of anti-fentanyl antibodies. The reagent was replaced, and, lo and behold, the measure of the antibody levels shot up.

FDA’s seal of approval and subsequent clinical trials are the only hurdles standing between the vaccine and availability for wide use.

If it’s approved, the vaccine will be administered via intramuscular injection. Meanwhile, Haile is developing a vaccine film administered under the tongue.

Of course, Haile is the first to admit FDA approval is a significant hurdle. But he’s also quick to point out that his team’s vaccine is almost entirely comprised of ingredients in other available vaccines, including ones for pneumonia and meningitis. Once on the market, it would be available for both people struggling with opioid use disorder and potentially first responders who come into contact with fentanyl users during their job.

At another point, vaccine components were clumping together during the synthesis. The team remedied that, too.

“There are issues we’ve had to solve over the years, but, fortunately, we’ve solved all of those,” Haile says.

He isn’t one to dwell on roadblocks. In fact, in conversation in mid-April, Haile was brimming with optimism. The team’s litany of tests thus far proves that the vaccine works in rats and mice, which means the

“People may get discouraged when they see this won’t be on the market for a few more years, but I want to point out that the individuals in our clinical trials will benefit,” Haile says. “I’ve been contacted by numerous folks around the United States wanting to be in this trial, probably hundreds—mostly parents who desperately want to help their kids address their addiction or prevent them from overdosing and potentially dying.”

“I know this vaccine,” he concludes, “will save lives.”