Preclinical Efficacy and Selectivity of Vaccines Targeting Fentanyl, Alfentanil, Sufentanil, and Acetylfentanyl in Rats

Carly Baehr, Christine Robinson, Andrew Kassick, Rajwana Jahan, Valeria Gradinati, Saadyah E. Averick, Scott P. Runyon, Marco Pravetoni

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The ongoing public health emergency of opioid use disorders (OUD) and overdose in the United States is largely driven by fentanyl and its related analogues and has resulted in over 75 673 deaths in 2021. Immunotherapeutics such as vaccines have been investigated as a potential interventional strategy complementary to current pharmacotherapies to reduce the incidence of OUD and opioid-related overdose. Given the importance of targeting structurally distinct fentanyl analogues, this study compared a previously established lead conjugate vaccine (F1-CRM) to a series of novel vaccines incorporating haptens derived from alfentanil and acetylfentanyl (F8, 9a, 9b, 10), and evaluated their efficacy against drug-induced pharmacological effects in rats. While no vaccine tested provided significant protection against alfentanil, lead formulations were effective in reducing antinociception, respiratory depression, and bradycardia elicited by fentanyl, sufentanil, and acetylfentanyl. Compared with control, vaccination with F1-CRM also reduced drug levels in the brain of rats challenged with lethal doses of fentanyl. These data further support investigation of F1-CRM as a candidate vaccine against fentanyl and selected analogues.

Original languageEnglish (US)
Pages (from-to)6584-16592
Number of pages10009
JournalACS Omega
Volume7
Issue number19
DOIs
StatePublished - May 17 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 grant UG3-DA048386 (M.P.).

Publisher Copyright:
© 2022 The Authors. Published by American Chemical Society.

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