Efficacy and Selectivity of Monovalent and Bivalent Vaccination Strategies to Protect against Exposure to Carfentanil, Fentanyl, and Their Mixtures in Rats

Bethany Crouse, Mariah M. Wu, Valeria Gradinati, Andrew J. Kassick, Daihyun Song, Rajwana Jahan, Saadyah Averick, Scott Runyon, Sandra D. Comer, Marco Pravetoni

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Drug-related fatal overdoses have significantly increased in the past decade due to the widespread availability of illicit fentanyl and other potent synthetic opioids such as carfentanil. Deliberate or accidental consumption or exposure to carfentanil, fentanyl, and their mixture induces respiratory depression and bradycardia that can be difficult to reverse with the opioid receptor antagonist naloxone. Vaccines offer a promising strategy to reduce the incidence of fatalities associated with fentanyl-related substances, as well as treatment for opioid use disorder (OUD). This study reports monovalent and bivalent vaccination strategies that elicit polyclonal antibody responses effective in protecting against the pharmacological actions of carfentanil, fentanyl, or carfentanil/fentanyl mixtures. Rats were prophylactically immunized with individual conjugate vaccines containing either carfentanil- or fentanyl-based haptens, or their combination in bivalent vaccine formulations, and then challenged with carfentanil, fentanyl, or their mixture. First, these studies identified a lead vaccine protective against carfentanil-induced antinociception, respiratory depression, and bradycardia. Then, efficacy against both carfentanil and fentanyl was achieved through bivalent vaccination strategies that combined lead anti-carfentanil and anti-fentanyl vaccines via either heterologous prime/boost or co-administration immunization regimens. These preclinical data support the development of vaccines as a viable strategy to prevent toxicity from exposure to excessive doses of carfentanil, fentanyl, or their mixtures.

Original languageEnglish (US)
Pages (from-to)331-343
Number of pages13
JournalACS Pharmacology and Translational Science
Issue number5
StatePublished - May 13 2022

Bibliographical note

Funding Information:
This work was supported by the National Institute on Drug Abuse (NIDA) and the National Institute of Neurological Disorders and Stroke (NINDS) under award numbers UG3DA048386 (M.P.), T32DA007097 (M.M.W. and B.C.), and F31DA054760 (B.C.), and the University of Minnesota Graduate Program in Pharmacology (D.S.). We thank our Scientific Officer Dr. Jason Sousa from the Division of Therapeutics and Medical Consequences from NIDA.

Publisher Copyright:
© 2022 American Chemical Society.


  • carfentanil
  • fentanyl
  • multivalent
  • opioid use disorder
  • overdose
  • vaccine

PubMed: MeSH publication types

  • Journal Article


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