TY - JOUR
T1 - Preclinical Efficacy and Selectivity of Vaccines Targeting Fentanyl, Alfentanil, Sufentanil, and Acetylfentanyl in Rats
AU - Baehr, Carly
AU - Robinson, Christine
AU - Kassick, Andrew
AU - Jahan, Rajwana
AU - Gradinati, Valeria
AU - Averick, Saadyah E.
AU - Runyon, Scott P.
AU - Pravetoni, Marco
N1 - 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.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
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U2 - 10.1021/acsomega.2c00820
DO - 10.1021/acsomega.2c00820
M3 - Article
C2 - 35601290
AN - SCOPUS:85129631540
SN - 2470-1343
JO - ACS Omega
JF - ACS Omega
ER -
