The Pravetoni Lab focuses on developing and translating biologic countermeasures, primarily vaccines and monoclonal antibodies, to prevent and treat substance use disorders (SUD), opioid use disorder (OUD), and overdose, while also building broader platforms relevant to other chemical and biological threats.
The lab’s work at Hennepin Healthcare Research Institute and the University of Minnesota concentrated on establishing and refining hapten–carrier conjugate vaccines targeting prescription and illicit opioids such as oxycodone and hydrocodone. These studies helped demonstrate that opioid-specific antibodies can sequester drug in the periphery, reduce brain exposure, and blunt behavioral and toxic effects in rodent models. In parallel, the group published a field-defining review outlining how opioid vaccines could fit alongside existing medications for OUD and reduce overdose mortality, framing many of the mechanistic and translational questions that have guided the lab’s subsequent work.
The lab has since expanded its focus to powerful synthetic opioids, particularly fentanyl and its analogs. Using medicinal chemistry and protein engineering, the group helped generate and characterize high-affinity monoclonal antibodies (mAbs) that selectively bind fentanyl, alter its pharmacokinetics, and protect against respiratory depression and lethality in preclinical models. This included first-in-class chimeric antibodies capable of neutralizing multiple fentanyl analogs, providing a proof-of-concept biologic that could complement or extend naloxone in treating overdose. In parallel, vaccine platforms against heroin and other opioids continued to be optimized and advanced toward human testing, contributing to the first experimental opioid vaccine evaluated in a U.S. phase 1a/1b clinical trial.
After Dr. Pravetoni’s move to the University of Washington, the lab’s work increasingly emphasized translation: advancing lead opioid vaccines and mAbs from rodent models into large animals and toward clinical development. Structure-guided engineering and humanization of anti-fentanyl mAbs refined binding properties and developability to meet regulatory expectations for first-in-human studies. In parallel, the group’s vaccine efforts incorporated novel adjuvants (including TLR4 and TLR7/8 agonists) and nanoparticle delivery systems to boost immunogenicity and durability of protection against fentanyl challenge, overdose, and self-administration in rats and miniature pigs.
The lab has also built a broader program around mechanisms and biomarkers that predict or modulate vaccine and mAb efficacy, examining innate and adaptive immune responses, adjuvant effects, and delivery platforms such as lipid–polymer hybrid nanoparticles and virus-like particles. This mechanistic work underpins next-generation formulations targeting multiple opioid classes and informs parallel projects on vaccines, mAbs, and diagnostics for infectious diseases and other chemical threats.
Today, as part of UW Psychiatry & Behavioral Sciences and the Center for Medication Development for Substance Use Disorders and Overdose, the Pravetoni Lab leads a heavily NIH-funded translational portfolio that spans discovery, preclinical development, and early clinical translation of opioid-targeted vaccines and monoclonal antibodies. Their work has helped establish immune-pharmacotherapy as a realistic strategy to prevent relapse, reduce overdose risk, and provide new tools against the evolving synthetic opioid crisis, while creating platforms that can be adapted to future drugs of abuse and other high-impact threats.