Efficacy of conjugate vaccines containing divalent haptens compared to monovalent and admixture vaccines against fentanyl and carfentanil in rats

Abstract ID 91887 Poster Board 279 Opioid use disorder (OUD) currently affects an estimated 2.7 million individuals in the US. With more than 80% of fatal overdoses involving opioids such as fentanyl and its potent analogs, there is a need for improved therapeutics for treating OUD and preventing overdose. Previously, anti-opioid conjugate vaccines have shown promise in pre-clinical studies and have demonstrated efficacy in reducing the effects of fentanyl and its analogs, including carfentanil. Importantly, such vaccines show selectivity for the target opioid based on the chemical structure of the hapten, suggesting that efficacy of conjugate vaccines against multiple fentanyl analogs could be enhanced by utilizing haptens with structures mimicking other analogs of interest. This study evaluated the efficacy of conjugate vaccines that contained haptens based on either fentanyl or carfentanil, and compared them against vaccines containing novel divalent haptens intended to target both drugs simultaneously. Rats (Sprague Dawley, n = 6 per group) were immunized with fentanyl- or carfentanil-targeting monovalent conjugate vaccines, an admixture vaccine containing a combination of the monovalent vaccines, or a novel divalent vaccine. All vaccines were formulated with alum adjuvant and administered intramuscularly every two weeks for a total of four immunizations. Efficacy of vaccines was evaluated against fentanyl, carfentanil, and their mixture; and opioid-induced antinociception and respiratory depression were monitored. While vaccines containing divalent haptens reduced the distribution of fentanyl and carfentanil mixtures to brain, as well as their antinociceptive and respiratory effects, the admixture vaccine was more effective than either divalent vaccine. These results suggest that optimization of individual vaccines targeting specific opioids may be a more effective approach than simultaneous targeting of multiple drugs. This work was supported by NIDA under UG3DA048386.