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A TLR7/8 agonist increases efficacy of anti-fentanyl vaccines in rodent and porcine models

Opioid use disorders (OUD) and overdose are public health threats worldwide. Widespread access to highly potent illicit synthetic opioids such as fentanyl is driving the recent rise in fatal overdoses. Vaccines containing fentanyl-based haptens conjugated to immunogenic carrier proteins offer a long...

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Autores principales: Crouse, Bethany, Miller, Shannon M., Muelken, Peter, Hicks, Linda, Vigliaturo, Jennifer R., Marker, Cheryl L., Guedes, Alonso G. P., Pentel, Paul R., Evans, Jay T., LeSage, Mark G., Pravetoni, Marco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10366150/
https://www.ncbi.nlm.nih.gov/pubmed/37488109
http://dx.doi.org/10.1038/s41541-023-00697-9
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author Crouse, Bethany
Miller, Shannon M.
Muelken, Peter
Hicks, Linda
Vigliaturo, Jennifer R.
Marker, Cheryl L.
Guedes, Alonso G. P.
Pentel, Paul R.
Evans, Jay T.
LeSage, Mark G.
Pravetoni, Marco
author_facet Crouse, Bethany
Miller, Shannon M.
Muelken, Peter
Hicks, Linda
Vigliaturo, Jennifer R.
Marker, Cheryl L.
Guedes, Alonso G. P.
Pentel, Paul R.
Evans, Jay T.
LeSage, Mark G.
Pravetoni, Marco
author_sort Crouse, Bethany
collection PubMed
description Opioid use disorders (OUD) and overdose are public health threats worldwide. Widespread access to highly potent illicit synthetic opioids such as fentanyl is driving the recent rise in fatal overdoses. Vaccines containing fentanyl-based haptens conjugated to immunogenic carrier proteins offer a long-lasting, safe, and cost-effective strategy to protect individuals from overdose upon accidental or deliberate exposure to fentanyl and its analogs. Prophylactic or therapeutic active immunization with an anti-fentanyl vaccine induces the production of fentanyl-specific antibodies that bind the drug in the blood and prevent its distribution to the brain, which reduces its reinforcing effects and attenuates respiratory depression and bradycardia. To increase the efficacy of a lead anti-fentanyl vaccine, this study tested whether the incorporation of synthetic toll-like receptor (TLR) 4 and TLR7/8 agonists as vaccine adjuvants would increase vaccine efficacy against fentanyl challenge, overdose, and self-administration in either rats or Hanford miniature pigs. Formulation of the vaccine with a nucleolipid TLR7/8 agonist enhanced its immunogenicity and efficacy in preventing fentanyl-induced respiratory depression, analgesia, bradycardia, and self-administration in either rats or mini-pigs. These studies support the use of TLR7/8 adjuvants in vaccine formulations to improve their clinical efficacy against OUD and potentially other substance use disorders (SUD).
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spelling pubmed-103661502023-07-26 A TLR7/8 agonist increases efficacy of anti-fentanyl vaccines in rodent and porcine models Crouse, Bethany Miller, Shannon M. Muelken, Peter Hicks, Linda Vigliaturo, Jennifer R. Marker, Cheryl L. Guedes, Alonso G. P. Pentel, Paul R. Evans, Jay T. LeSage, Mark G. Pravetoni, Marco NPJ Vaccines Article Opioid use disorders (OUD) and overdose are public health threats worldwide. Widespread access to highly potent illicit synthetic opioids such as fentanyl is driving the recent rise in fatal overdoses. Vaccines containing fentanyl-based haptens conjugated to immunogenic carrier proteins offer a long-lasting, safe, and cost-effective strategy to protect individuals from overdose upon accidental or deliberate exposure to fentanyl and its analogs. Prophylactic or therapeutic active immunization with an anti-fentanyl vaccine induces the production of fentanyl-specific antibodies that bind the drug in the blood and prevent its distribution to the brain, which reduces its reinforcing effects and attenuates respiratory depression and bradycardia. To increase the efficacy of a lead anti-fentanyl vaccine, this study tested whether the incorporation of synthetic toll-like receptor (TLR) 4 and TLR7/8 agonists as vaccine adjuvants would increase vaccine efficacy against fentanyl challenge, overdose, and self-administration in either rats or Hanford miniature pigs. Formulation of the vaccine with a nucleolipid TLR7/8 agonist enhanced its immunogenicity and efficacy in preventing fentanyl-induced respiratory depression, analgesia, bradycardia, and self-administration in either rats or mini-pigs. These studies support the use of TLR7/8 adjuvants in vaccine formulations to improve their clinical efficacy against OUD and potentially other substance use disorders (SUD). Nature Publishing Group UK 2023-07-24 /pmc/articles/PMC10366150/ /pubmed/37488109 http://dx.doi.org/10.1038/s41541-023-00697-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Crouse, Bethany
Miller, Shannon M.
Muelken, Peter
Hicks, Linda
Vigliaturo, Jennifer R.
Marker, Cheryl L.
Guedes, Alonso G. P.
Pentel, Paul R.
Evans, Jay T.
LeSage, Mark G.
Pravetoni, Marco
A TLR7/8 agonist increases efficacy of anti-fentanyl vaccines in rodent and porcine models
title A TLR7/8 agonist increases efficacy of anti-fentanyl vaccines in rodent and porcine models
title_full A TLR7/8 agonist increases efficacy of anti-fentanyl vaccines in rodent and porcine models
title_fullStr A TLR7/8 agonist increases efficacy of anti-fentanyl vaccines in rodent and porcine models
title_full_unstemmed A TLR7/8 agonist increases efficacy of anti-fentanyl vaccines in rodent and porcine models
title_short A TLR7/8 agonist increases efficacy of anti-fentanyl vaccines in rodent and porcine models
title_sort tlr7/8 agonist increases efficacy of anti-fentanyl vaccines in rodent and porcine models
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10366150/
https://www.ncbi.nlm.nih.gov/pubmed/37488109
http://dx.doi.org/10.1038/s41541-023-00697-9
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