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Opioid use disorder (OUD) and opioid overdose are growing problems. Opioid vaccines are a novel treatment approach for OUD, but current vaccine strategies are slow to elicit antibodies and require multiple immunizations. Here, we report our efforts to engineer opioid vaccines that could elicit high-titer, long-lasting antibodies with a single dose. We used bacteriophage Q beta virus-like particles (VLPs) as a platform to display oxycodone in a highly immunogenic format. Opioid drugs of interest were chemically modified to include a short peptide linker (G-G-G- G-C). This allowed for the chemical conjugation of the opioid drugs to the surface of the Q beta VLPs. These drug- VLP conjugates were then used to immunize mice one time intramuscularly. Sera was collected from the immunized mice at days 3, 7, and 14 post immunization. Sera were then assessed by enzyme-linked immunosorbent assay (ELISA) for antibodies against oxycodone to determine the kinetics of the antibody response elicited by our vaccines. Additionally, mice were challenged with a lethal overdose of oxycodone at day 16 post immunization and survival of immunized and control mice were compared. Sera from mice immunized with Q beta oxycodone elicited antibodies as quickly as 3 days post-immunization. Male, but not female, mice challenged with a lethal overdose of oxycodone showed statistically significant protection. Future studies will investigate our vaccination strategy for other opioids, the impact of boost on protection, and protection from drug-induced antinociception upon sub-lethal oxycodone administration.


Poster presented at the Brain & Behavioral Health Research Day 2021



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