Enhancing Protective Antibodies against Opioids through Antigen Display on Virus-like Particles

Opioid use disorder (OUD) has become a public health crisis, with recent significant increases in the number of deaths due to overdose. Vaccination can provide an attractive complementary strategy to combat OUD. A key for high vaccine efficacy is the induction of high levels of antibodies specific to the drug of abuse. Herein, a powerful immunogenic carrier, virus-like particle mutant bacteriophage Qβ (mQβ), has been investigated as a carrier of a small molecule hapten 6-AmHap mimicking heroin. The mQβ-6-AmHap conjugate was able to induce significantly higher levels of IgG antibodies against 6-AmHap than mice immunized with the corresponding tetanus toxoid-6-AmHap conjugate in head-to-head comparison studies in multiple strains of mice. The IgG antibody responses were persistent with high anti-6-AmHap titers 600 days after being immunized with mQβ-6-AmHap. The antibodies induced exhibited strong binding toward multiple heroin/morphine derivatives that have the potential to be abused, while binding weakly to medications used for OUD treatment and pain relief. Furthermore, vaccination effectively reduced the impacts of morphine on mice in both ambulation and antinociception assays, highlighting the translational potential of the mQβ-6-AmHap conjugate to mitigate the harmful effects of drugs of abuse.