“We don’t have to keep playing catch-up with every new synthetic designer drug that emerges,” says Kim Janda, a chemistry professor at Scripps Research. His lab has built an experimental vaccine that trains the body to attack fentanyl before the drug gets near the brain.
Janda holds the Ely R. Callaway, Jr. Professorship in Chemistry and is senior author of the work, which appeared in the Journal of Medicinal Chemistry. His group had already made vaccine candidates against fentanyl and heroin. Those designs share a weakness. They need the drug itself, or a close copy, to teach the immune system, and the drugs are tightly regulated. The immune response also tends to be narrow, so it may recognize only the exact compound used.
Black-market chemists make that narrowness a problem. “They are constantly coming up with new versions to skirt regulations and avoid detection in standard screenings,” Janda says.
A molecule that looks different
The team tried the opposite approach. Earlier, Janda’s lab had made a modified form of fentanyl that kept its pain relief but lost many of its harmful side effects. For the vaccine, they tested a related molecule with a different core structure that shared only some components with fentanyl.
“We honestly didn’t know if it would work,” said Arran Stewart, a research associate in the lab and first author. “The conventional wisdom says that to get the immune system to recognize fentanyl, you have to use something that looks like fentanyl. We were doing the opposite.”
They bound the molecule to a carrier protein and vaccinated mice with four doses over eight weeks. The immune system did not need an exact match. It picked up a general molecular signature common to the fentanyl class.
Results in mice
Antibodies from the mice bound tightly to fentanyl, carfentanil, China White, acetylfentanyl and furanylfentanyl. They left alone morphine, oxycodone, remifentanil and alfentanil, all used in medicine.
When vaccinated mice were given fentanyl doses that would normally cause severe respiratory depression, their breathing stayed nearly normal. Brain fentanyl levels were roughly 70 percent lower than in mice that got no vaccine.
Clinical trials are still needed to test safety and effectiveness in people. Janda says the platform could one day protect people in recovery programs and others at high risk of exposure. The Shadek Family Foundation supported the work, and Lisa Eubanks, Bin Zhou and Rachel Steinhardt of Scripps are co-authors. Consult your doctor for medical advice.
Sources
- New fentanyl vaccine blocks deadly overdoses before they start
- Experimental vaccine protects against fentanyl and related opioids
