Therapeutic and Prophylactic Vaccines to Counteract Fentanyl Use Disorders and Toxicity

Overview

Journal J Med Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2020 Nov 20

PMID 33215913

Citations 24

Authors

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

Affiliations

Soon will be listed here.

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.

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