Pre-clinical safety and toxicology profile of a candidate vaccine to treat oxycodone use disorder

Fatima A Hamid, Cheryl L. Marker, Michael D. Raleigh, Aaron Khaimraj, Scott Winston, Paul R Pentel, Marco Pravetoni

Research output: Contribution to journalArticlepeer-review


Opioid use disorders (OUD) and overdose represent a public health threat, resulting in thousands of deaths annually worldwide. Vaccines offer a promising treatment for OUD and potentially the prevention of fatal overdoses. The Oxy(Gly)4-sKLH Conjugate Vaccine, Adsorbed (Oxy(Gly)4-sKLH) has shown promising pre-clinical efficacy at reducing the behavioral and pharmacological effects of oxycodone. To support its clinical evaluation, a GLP toxicology study was performed to address the safety of Oxy(Gly)4-sKLH. Sprague Dawley rats were vaccinated with either aluminum adjuvant (alum) or vaccine adsorbed on alum. Low and high doses of Oxy(Gly)4-sKLH, equivalent to a 1X or 47X human dose, respectively, were administered every two weeks for a total of four vaccinations. Both vaccine doses induced high antibody titers. Vaccine-related toxicity was assessed postmortem in one experimental group after receiving the fourth immunization of the vaccine's high dose. For the remaining experimental groups, rats were challenged with 1.5 mg/kg/day s.c. oxycodone for 7 days after the fourth vaccination to assess whether concurrent exposure to oxycodone in vaccinated animals resulted in toxicity. All rats, except a subset of the aluminum control and the high dose vaccine groups, were sacrificed following oxycodone exposure. These subsets were allowed a four weeks recovery period prior to euthanasia. In this study, no Oxy(Gly)4-sKLH-related hematology, clinical chemistry, urinalysis, body weight, organ weight, or anatomic pathology toxicological findings were observed. These results demonstrate that the Oxy(Gly)4-sKLH vaccine is well tolerated, is immunogenic even at low doses, and does not produce undesired side effects in rats.

Original languageEnglish (US)
Pages (from-to)3244-3252
Number of pages9
Issue number23
StatePublished - May 20 2022

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health National Institute on Drug Abuse [Grants U01DA038876 (M.P. and P.R.P and UG3DA047711 (M.P.)]. S.W. received compensation as an independent consultant on this study and he is the sole proprietor of Winston Biopharmaceutical Consulting.

Publisher Copyright:
© 2022 Elsevier Ltd


  • FDA
  • GLP
  • IND
  • Opioid
  • Opioid use disorder
  • Oxycodone
  • Safety
  • Toxicity
  • Vaccine


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