A new vaccine designed to protect against oxycodone has demonstrated the ability to generate antibodies in the blood, preventing the drug from reaching the brain by trapping it in the bloodstream. The study, funded by the California National Primate Research Center’s Pilot Research Program at the University of California, Davis, examined this promising treatment option for a disorder affecting nearly three million people in the United States. The findings suggest that the vaccine could be a candidate for human use.

As part of the CNPRC’s pilot research program, Kathryn Frietze, an assistant professor in the Department of Molecular Genetics and Microbiology at the University of New Mexico School of Medicine, and graduate student, Isabella Romano, assessed the newly engineered vaccine’s protective abilities in two animal models. “We believe that vaccines could be a viable treatment option for both OUD and opioid overdose,” said Romano. The study also examined the vaccine’s interactions with two other Opioid Use Disorder (OUD) treatments, Methadone and Buprenorphine.

“We believe that vaccines could be a viable treatment option for both OUD and opioid overdose” – Romano

Despite drugs like Narcan, which can reverse the effects of an opioid overdose, becoming available over the counter, opioid overdose deaths continue to rise. Unfortunately, Narcan relies on bystander awareness and quick action to be effective. Other treatments like methadone carry a significant stigma and require access to medical care. Recent studies indicate that immunotherapies, such as vaccines, may offer a way to overcome the challenges associated with current treatment options.

How does it work?
When a drug is introduced to the bloodstream, it must pass through a specialized filter called the blood-brain barrier to reach the brain. Once in the brain, the drug binds to its specific receptors to elicit an effect. A vaccine can interfere with both processes. By stimulating the production of antibodies that recognize the drug and bind to it the vaccine hinders the drug’s ability to cross the barrier. The antibody also blocks the drug’s ability to bind to its receptor by occupying the specific binding site.

Findings from the current study showed the vaccine was successful in increasing antibody levels in the bloodstream of mice and nonhuman primates. Importantly, the antibodies bound to oxycodone without causing any adverse health outcomes. When the vaccine was challenged with the administration of oxycodone, results showed high levels of the drug in remained in the blood and limited evidence of “free” oxycodone that could reach the brain.

A practical option for clinics
The vaccine also retained the ability to elicit antibodies following various temperature fluctuations, highlighting its practical advantage for use in clinics. Analyses showed a minimal amount of cross-reactivity between the vaccine and Buprenorphine and no effect on Methadone, indicating that the vaccine could be used alongside current treatment plans.

“An important aspect of the development of opioid vaccines is considering concerns and acceptability issues from both patients and providers” – Romano

Next Steps
Now that the vaccine has demonstrated safety in nonhuman primates, Frietze and colleagues will continue testing its protective capacity. While blood analyses are promising, future studies will investigate how well the vaccine protects against the effects of oxycodone in the nervous system, such as respiratory depression and the blockade of pain. Researchers will also explore whether vaccinated animals remain sensitive to other OUD treatments.

“An important aspect of the development of opioid vaccines is considering concerns and acceptability issues from both patients and providers”, Romano explains. The lab is currently investigating these potential obstacles in hopes that vaccines for drugs of abuse will be increasingly seen as a viable treatment option with minimal stigma and maximal accessibility.

Written by: Logan Savidge

Romano IG, Core SB, Lee NR, Mowry C, Van Rompay KKA, Huang Y, Chackerian B, Frietze KM. A bacteriophage virus-like particle vaccine against oxycodone elicits high-titer and long-lasting antibodies that sequester drug in the blood. Vaccine. 2023 Dec 29:S0264-410X(23)01533-5. doi: 10.1016/j.vaccine.2023.12.077. Epub ahead of print. PMID: 38160131.

Corresponding author
E-mail address: kfrietze@salud.unm.edu (K.M. Frietze).

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