In the spring of 2020, a team of researchers from the University of Minnesota Medical School approached Dr. Alonso Guedes of the University of Minnesota College of Veterinary Medicine (CVM) with a pressing challenge: they needed pigs to respond to opioids in a way that mimics human reactions, something pigs don’t naturally do.
“Pigs are really similar to people in many ways, especially their immune systems, which makes them a great model to study human medicine,” says Guedes, professor of anesthesia and associate dean for research at CVM. “However, pigs are not very sensitive to the respiratory effects of opioids, and that poses a problem when studying interventions for opioid overdoses.”
With overdose deaths still exceeding 100,000 annually in the U.S., and more than 70 percent involving opioids like fentanyl, Guedes' work has become crucial. His laboratory developed a method to make pigs more sensitive to opioids and has shared the model with researchers worldwide.
Through collaborations with several other universities, Guedes’ pig model is now central to developing tools to both prevent and treat overdoses.
A vaccine for opioid overdoses
One of the most promising efforts involves vaccines that could prevent an overdose in people with opioid use disorder (OUD), particularly during vulnerable periods when they are at high risk for relapse.
“The more a person takes opioids, the more tolerant they become, so they need higher and higher doses to get high. But if they go for a period of time without taking opioids, that tolerance reverses back to normal. If they take the same amount then, they overdose,” Guedes says.
To trigger an immune response, researchers chemically attach a molecule the body recognizes as foreign to the opioid—commonly fentanyl. This version teaches the immune system to see the drug as a threat and build antibodies against it.
The vaccines are opioid-specific—targeting fentanyl, heroin, or other compounds—so they won’t interfere with pain treatment when medically necessary.
Given his expertise with animal medicine, Guedes was able to get pigs to respond to an opioid overdose as humans do and serve as a model for how the vaccines may work in humans. It’s a crucial step in the drug development process since the Food and Drug Administration requires animal studies to show the drug is safe and effective before being used in humans. Early results have been promising, with the team now conducting toxicology studies, one of the final stages before moving into human testing.
“It’s a painstaking process,” Guedes says. “By the time we start studying it in humans, we know as much as we can about the vaccines.”
Treating overdoses that do happen
When overdoses occur, people often stop breathing. Guedes’ team is developing a patch placed on the neck that delivers electrical pulses to stimulate the nerves controlling the respiratory system.
“Having a technology that does not care about what kind of drug someone took that made them stop breathing can be very helpful,” he says. “That’s where this respiratory device comes into play.”
The first studies in pigs are complete, and the team is now refining the design.
Together, these innovations—vaccines, antibodies, and medical devices—represent a multi-pronged, research-driven response to one of the most urgent public health crises of our time.
