Therapeutic and Prophylactic Vaccines to Counteract Fentanyl Use Disorders and Toxicity

Christine Robinson, Valeria Gradinati, Fatima Hamid, Carly Baehr, Bethany Crouse, Saadyah Averick, Marina Kovaliov, Danni Harris, Scott Runyon, Federico Baruffaldi, Mark LeSage, Sandra Comer, Marco Pravetoni

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The incidence of fatal overdoses has increased worldwide due to the widespread access to illicit fentanyl and its potent analogues. Vaccines offer a promising strategy to reduce the prevalence of opioid use disorders (OUDs) and to prevent toxicity from accidental and deliberate exposure to fentanyl and its derivatives. This study describes the development and characterization of vaccine formulations consisting of novel fentanyl-based haptens conjugated to carrier proteins. Vaccine efficacy was tested against opioid-induced behavior and toxicity in mice and rats challenged with fentanyl and its analogues. Prophylactic vaccination reduced fentanyl- and sufentanil-induced antinociception, respiratory depression, and bradycardia in mice and rats. Therapeutic vaccination also reduced fentanyl intravenous self-administration in rats. Because of their selectivity, vaccines did not interfere with the pharmacological effects of commonly used anesthetics nor with methadone, naloxone, oxycodone, or heroin. These preclinical data support the translation of vaccines as a viable strategy to counteract fentanyl use disorders and toxicity.

Original languageEnglish (US)
Pages (from-to)14647-14667
Number of pages21
JournalJournal of medicinal chemistry
Volume63
Issue number23
DOIs
StatePublished - Dec 10 2020

Keywords

  • Animals
  • Bacterial Proteins/chemistry
  • Cattle
  • Diphtheria Toxin/chemistry
  • Female
  • Fentanyl/immunology
  • Haptens/chemistry
  • Hemocyanins/chemistry
  • Male
  • Mice, Inbred BALB C
  • Opioid-Related Disorders/prevention & control
  • Piperidines/chemical synthesis
  • Proof of Concept Study
  • Rats, Sprague-Dawley
  • Serum Albumin, Bovine/chemistry
  • Sufentanil/immunology
  • Vaccines/immunology

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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