Divalent Vaccination to Protect Against the Cardiopulmonary and Antinociceptive Effects of Fentanyl, Oxycodone, and their Mixture in Male Rats

Abstract ID 101638 Poster Board 313 The opioid overdose epidemic continues to worsen despite the availability of reversal agents. Although much work has been done developing vaccines targeting individual drugs, targeting multiple drugs may provide greater clinical utility given the prevalence of polydrug use. Thus, the current studies evaluated the cardiopulmonary and antinociceptive effects of fentanyl, oxycodone, and a fentanyl+oxycodone mixture in rats vaccinated with divalent vaccine formulations targeting both drugs. Male rats were vaccinated with either monovalent or divalent vaccine formulations, targeting fentanyl, oxycodone, or both, respectively. Subsequently, the cardiopulmonary and antinociceptive effects of fentanyl (0.1 mg/kg), oxycodone (4.5 mg/kg), and a mixture of fentanyl (0.05 mg/kg) and oxycodone (2.25 mg/kg) were evaluated, with brains and blood being harvested following the terminal challenge for subsequent analyses via liquid chromatography mass spectrometry. Rats vaccinated with the divalent vaccine displayed significant protection against the respiratory depressive and antinociceptive effects of fentanyl and oxycodone, whereas rats vaccinated with either the fentanyl or oxycodone vaccines were protected against the effects of fentanyl or oxycodone, respectively. Consistent with this, when administered in a mixture, fentanyl and oxycodone were both significantly sequestered in the serum of rats vaccinated with the divalent formulation. These data add to the growing body of literature demonstrating the potential of vaccines to help protect against opioid overdose. Future studies will evaluate the ability of divalent vaccines to attenuate other abuse-related effects of drug mixtures with the ultimate goal of developing treatments that protect against common drug use patterns and scenarios.