Multivalent Vaccination against Polydrug Use in Opioid Use Disorder

Abstract

<b>Abstract ID 23682</b> <b>Poster Board 353</b> More than 107,000 cases of fatal drug overdose were reported in 2021, with around 70% of cases involving opioids. Individuals with opioid use disorder often administer polydrug street mixtures that contain multiple opioids (fentanyl and oxycodone) and non-opioids (including stimulants such as methamphetamine), leading to detrimental health outcomes. Active vaccination is being pursued as a treatment against substance use disorders (including fentanyl, carfentanil, oxycodone, heroin, and methamphetamine) and has shown efficacy in preclinical models, although the efficacy against polydrug use is not well established. To develop these vaccines, conjugates consisting of haptens crosslinked to immunogenic carrier proteins induce the T-cell-dependent generation of hapten-specific antibodies. These antibodies bind to target drugs in the circulatory system and block the drugs from crossing the blood-brain barrier, attenuating drug effects in the central nervous system. Previously, four monovalent vaccines against four different opioids have been co-administered as a quadrivalent vaccine without decreasing their individual efficacy in mice. In the current study, these four monovalent vaccines were co-formulated in a single syringe and injected into Sprague Dawley rats as a new vaccination regimen. Results showed that co-formulated quadrivalent vaccination induced greater drug-specific serum IgG titers and reduced drug distribution to the brain to a greater extent than co-administering individual vaccines at different injection sites. In addition, adding a stimulant conjugate vaccine as a pentavalent formulation did not decrease the efficacy of the quadrivalent vaccine against opioids. The combined results show that different conjugate vaccines can be co-formulated as multivalent vaccines to provide protection against polydrug use by different classes of drugs and suggest a potential therapeutic to reduce overdose related to polydrug use. This work was supported by the National Institute on Drug Abuse Grants UG3DA048386