Functional in vivo characteristics of antibodies generated by an oxycodone vaccine

Abstract

An oxycodone vaccine (OXY‐sKLH) is being developed to treat opioid use disorder. OXY‐sKLH has been demonstrated to be effective at blocking clinically relevant doses of oxycodone and reducing its reinforcing efficacy. To further assess the potential of OXY‐sKLH for clinical use, critical in vivo properties of the vaccine were studied. Sprague Dawley rats were vaccinated with OXY‐sKLH or control vaccine (sKLH alone) in alum adjuvant. Exposure of vaccinated rats to oxycodone weekly confirmed the expectation that oxycodone alone does not boost oxycodone‐specific antibody titers in vaccinated rats. Re‐vaccination with OXY‐sKLH was necessary to maintain titers. In a separate experiment, antibody titers of vaccinated rats showed a titer of 1.6 × 105 after the final vaccine dose which declined to 0.54 × 105 at 3 months. Vaccine specificity for oxycodone was assessed in vivo. Vaccination protected against oxycodone‐induced, but not methadone‐induced, antinociception. Administration of naloxone to vaccinated rats that had received methadone partially restored nociception and fully reversed respiratory depression. Vaccination of rats with OXY‐sKLH did not alter the pharmacokinetics or antinociception of subsequently administered fentanyl. These in vivo data confirm the previously reported in vitro specificity of this vaccine for oxycodone. Finally, vaccination with OXY‐sKLH extended oxycodone’s half‐life from 0.75 hr in control rats to 24 hr. Taken together, these results indicate that antibody titers generated by OXY‐sKLH are long lasting, and will not interfere with clinically useful non‐targeted opioids, and will decline even in the face of continued oxycodone exposure unless boosted by re‐vaccination. The prolonged oxycodone half‐life in vaccinated rats suggests the potential for antibody saturation if oxycodone exposure continues and is substantial and persistent.Support or Funding InformationThis work was supported by the National Institutes of Health National Institute on Drug Abuse [Grant U01DA038876] (to M.P. and P.R.P.)