Fentanyl conjugate vaccine by injected or mucosal delivery with dmLT or LTA1 adjuvants implicates IgA in protection from drug challenge

Abstract Fentanyl is a major contributor to the devastating increase in overdose deaths from substance use disorders (SUD). A vaccine targeting fentanyl could be a powerful immunotherapeutic. Here, we evaluated adjuvant and delivery strategies for conjugate antigen vaccination with fentanyl-based ha...

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Autores principales:	Addison E. Stone, Sarah E. Scheuermann, Colin N. Haile, Gregory D. Cuny, Marcela Lopez Velasquez, Joshua P. Linhuber, Anantha L. Duddupudi, Jennifer R. Vigliaturo, Marco Pravetoni, Therese A. Kosten, Thomas R. Kosten, Elizabeth B. Norton
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/644008cc7a484a358b436c0687cf30dc
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spelling	oai:doaj.org-article:644008cc7a484a358b436c0687cf30dc2021-12-02T16:50:27ZFentanyl conjugate vaccine by injected or mucosal delivery with dmLT or LTA1 adjuvants implicates IgA in protection from drug challenge10.1038/s41541-021-00329-02059-0105https://doaj.org/article/644008cc7a484a358b436c0687cf30dc2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00329-0https://doaj.org/toc/2059-0105Abstract Fentanyl is a major contributor to the devastating increase in overdose deaths from substance use disorders (SUD). A vaccine targeting fentanyl could be a powerful immunotherapeutic. Here, we evaluated adjuvant and delivery strategies for conjugate antigen vaccination with fentanyl-based haptens. We tested adjuvants derived from the heat-labile toxin of E. coli including dmLT and LTA1 by intramuscular, sublingual or intranasal delivery. Our results show anti-fentanyl serum antibodies and antibody secreting cells in the bone-marrow after vaccination with highest levels observed with an adjuvant (alum, dmLT, or LTA1). Vaccine adjuvanted with LTA1 or dmLT elicited the highest levels of anti-fentanyl antibodies, whereas alum achieved highest levels against the carrier protein. Vaccination with sublingual dmLT or intranasal LTA1 provided the most robust blockade of fentanyl-induced analgesia and CNS penetration correlating strongly to anti-FEN IgA. In conclusion, this study demonstrates dmLT or LTA1 adjuvant as well as mucosal delivery may be attractive strategies for improving the efficacy of vaccines against SUD.Addison E. StoneSarah E. ScheuermannColin N. HaileGregory D. CunyMarcela Lopez VelasquezJoshua P. LinhuberAnantha L. DuddupudiJennifer R. VigliaturoMarco PravetoniTherese A. KostenThomas R. KostenElizabeth B. NortonNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Addison E. Stone Sarah E. Scheuermann Colin N. Haile Gregory D. Cuny Marcela Lopez Velasquez Joshua P. Linhuber Anantha L. Duddupudi Jennifer R. Vigliaturo Marco Pravetoni Therese A. Kosten Thomas R. Kosten Elizabeth B. Norton Fentanyl conjugate vaccine by injected or mucosal delivery with dmLT or LTA1 adjuvants implicates IgA in protection from drug challenge
description	Abstract Fentanyl is a major contributor to the devastating increase in overdose deaths from substance use disorders (SUD). A vaccine targeting fentanyl could be a powerful immunotherapeutic. Here, we evaluated adjuvant and delivery strategies for conjugate antigen vaccination with fentanyl-based haptens. We tested adjuvants derived from the heat-labile toxin of E. coli including dmLT and LTA1 by intramuscular, sublingual or intranasal delivery. Our results show anti-fentanyl serum antibodies and antibody secreting cells in the bone-marrow after vaccination with highest levels observed with an adjuvant (alum, dmLT, or LTA1). Vaccine adjuvanted with LTA1 or dmLT elicited the highest levels of anti-fentanyl antibodies, whereas alum achieved highest levels against the carrier protein. Vaccination with sublingual dmLT or intranasal LTA1 provided the most robust blockade of fentanyl-induced analgesia and CNS penetration correlating strongly to anti-FEN IgA. In conclusion, this study demonstrates dmLT or LTA1 adjuvant as well as mucosal delivery may be attractive strategies for improving the efficacy of vaccines against SUD.
format	article
author	Addison E. Stone Sarah E. Scheuermann Colin N. Haile Gregory D. Cuny Marcela Lopez Velasquez Joshua P. Linhuber Anantha L. Duddupudi Jennifer R. Vigliaturo Marco Pravetoni Therese A. Kosten Thomas R. Kosten Elizabeth B. Norton
author_facet	Addison E. Stone Sarah E. Scheuermann Colin N. Haile Gregory D. Cuny Marcela Lopez Velasquez Joshua P. Linhuber Anantha L. Duddupudi Jennifer R. Vigliaturo Marco Pravetoni Therese A. Kosten Thomas R. Kosten Elizabeth B. Norton
author_sort	Addison E. Stone
title	Fentanyl conjugate vaccine by injected or mucosal delivery with dmLT or LTA1 adjuvants implicates IgA in protection from drug challenge
title_short	Fentanyl conjugate vaccine by injected or mucosal delivery with dmLT or LTA1 adjuvants implicates IgA in protection from drug challenge
title_full	Fentanyl conjugate vaccine by injected or mucosal delivery with dmLT or LTA1 adjuvants implicates IgA in protection from drug challenge
title_fullStr	Fentanyl conjugate vaccine by injected or mucosal delivery with dmLT or LTA1 adjuvants implicates IgA in protection from drug challenge
title_full_unstemmed	Fentanyl conjugate vaccine by injected or mucosal delivery with dmLT or LTA1 adjuvants implicates IgA in protection from drug challenge
title_sort	fentanyl conjugate vaccine by injected or mucosal delivery with dmlt or lta1 adjuvants implicates iga in protection from drug challenge
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/644008cc7a484a358b436c0687cf30dc
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Fentanyl conjugate vaccine by injected or mucosal delivery with dmLT or LTA1 adjuvants implicates IgA in protection from drug challenge

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