Fentanyl has become one of the deadliest drug epidemics our country has seen. Scripps Research is developing a new vaccine to help prevent fentanyl overdoses by stopping it before it hits the brain. Instead of targeting the drug itself, this vaccine will train the immune system to recognize a broad range of fentanyl-related drugs.
Currently, the only real treatment we have can only reverse an overdose after it’s started, and ideally, very soon after it’s started. In high doses, fentanyl and drugs like it disrupt brain function. This can result in your body suppressing vital signals that control things like breathing.
To be clear, a lethal dose of fentanyl for most people is pictured below.
Tiny, right? So you see how incredibly easy it could be to take or cut in with too much.
One of the biggest dangers with fentanyl is how often it is combined with other things. Often without the buyer’s knowledge. Some of these designer drugs are created to make fentanyl even more potent. Increasing the risk of an overdose.
“What this research shows us is that we don’t have to keep playing catch-up with every new synthetic designer drug that emerges,” says senior author Kim Janda, the Ely R. Callaway, Jr. Professor of Chemistry at Scripps Research. “By training the immune system to recognize the entire fentanyl class — not just individual structures — we can stay ahead of illicit drug traffickers.”
Vaccine Development
Most current vaccine development is looking for antibodies capable of binding to fentanyl in the bloodstream before it gets to the brain. The issue with that is that it relies on a molecule in the drug or very close to it. But that can result in the body only recognizing the exact strain of the drug used in the vaccine. They don’t recognize all of the modifications that often happen to it after. This makes any real-world applications very limited.
“The way the fentanyl landscape is evolving, the black-market drug makers are constantly coming up with new versions to skirt regulations and avoid detection in standard screenings,” explains Janda. “We need countermeasures that are going to work against all these future variants at once, not just one at a time.”
Janda and his team developed a modified version of fentanyl that cut out a lot of the drug’s side effects while maintaining its pain-relieving properties. This became the foundation for Scripps’ new vaccine since its core structure was completely different.
Testing
It was tested on mice over 8 weeks by attaching a carrier protein to the modified molecule. During this time, their bodies’ immune systems created antibodies that blocked a broader molecular signature shared by several fentanyl-related substances. Not only does it block fentanyl, but some variants, like carfentanil, China White, acetylfentanyl, and furanylfentanyl.
Despite hitting a broader range of drugs, the vaccine doesn’t seem to bind to many medical opioids. So medications like morphine, oxycodone, remifentanil, and alfentanil are unaffected.
Researchers also found that fentanyl levels in the brains of vaccinated mice were about 70% lower than in unvaccinated ones. Along with the animals, maintaining a normal breathing rate despite being given doses that normally cause severe respiratory depression.
The vaccine has not hit the human trial phase yet, but its positive impact could be immeasurable.
“The public health potential here is significant,” says Janda. “But so is the lesson that we can design vaccines that recognize an entire drug class, not just a singular drug.”
