“We don’t have to keep playing catch-up with every new synthetic designer drug that emerges.” That is how Kim Janda, a senior author at Scripps Research, describes what his lab’s experimental fentanyl vaccine could mean.
The vaccine is built to stop fentanyl before it reaches the brain. The findings appeared in the Journal of Medicinal Chemistry. Fentanyl shuts down the brain signals that drive breathing, and reversal drugs only work if someone gets them to the patient fast.
Why earlier vaccines fell short
Vaccines against fentanyl are not a new idea. The usual aim is to get the immune system to make antibodies that grab the drug in the blood. Janda’s lab has already worked on candidates for fentanyl and for heroin.
The trouble is how those vaccines are made. Most use the drug itself or a close molecular cousin to teach the immune system, and the drugs are tightly regulated, which makes the work harder. The immune response also tends to lock onto the one drug used in the vaccine. Black-market chemists keep tweaking fentanyl to dodge the law and raise its potency. “We need countermeasures that are going to work against all these future variants at once, not just one at a time,” Janda said.
A different starting molecule
His team started with a modified fentanyl molecule that kept the pain-relieving effect but cut the harmful side effects. It resembled fentanyl while having a different core structure. The researchers were doubtful it would work. They attached it to a carrier protein and gave mice four doses over eight weeks.
The antibodies that resulted recognized a broad molecular signature shared by fentanyl-related drugs, not an exact match to fentanyl. They picked out fentanyl, carfentanil, China White, acetylfentanyl and furanylfentanyl. They did not bind to morphine, oxycodone, remifentanil or alfentanil, which are prescribed opioids.
Vaccinated mice breathed nearly normally after doses of fentanyl that would normally cause severe respiratory depression. Fentanyl levels in their brains ran about 70 percent lower than in unvaccinated mice.
The work is still at the animal stage, and clinical trials will have to test safety and effectiveness in people. Janda sees possible use for people in recovery and for those at higher risk of exposure. “The public health potential here is significant,” he said. The Shadek Family Foundation funded the study.
