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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2021-05-01
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doaj-644008cc7a484a358b436c0687cf30dc2021-05-16T11:23:18ZengNature Publishing Groupnpj Vaccines2059-01052021-05-016111110.1038/s41541-021-00329-0Fentanyl conjugate vaccine by injected or mucosal delivery with dmLT or LTA1 adjuvants implicates IgA in protection from drug challengeAddison E. Stone0Sarah E. Scheuermann1Colin N. Haile2Gregory D. Cuny3Marcela Lopez Velasquez4Joshua P. Linhuber5Anantha L. Duddupudi6Jennifer R. Vigliaturo7Marco Pravetoni8Therese A. Kosten9Thomas R. Kosten10Elizabeth B. Norton11Department of Microbiology and Immunology, Tulane University School of MedicineDepartment of Microbiology and Immunology, Tulane University School of MedicineDepartment of Psychology, University of HoustonDepartment of Pharmacological & Pharmaceutical Sciences, University of HoustonDepartment of Microbiology and Immunology, Tulane University School of MedicineDepartment of Microbiology and Immunology, Tulane University School of MedicineDepartment of Pharmacological & Pharmaceutical Sciences, University of HoustonDepartment of Pharmacology, University of Minnesota Medical SchoolDepartment of Pharmacology, University of Minnesota Medical SchoolDepartment of Psychology, University of HoustonDepartment of Psychology, University of HoustonDepartment of Microbiology and Immunology, Tulane University School of MedicineAbstract 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.https://doi.org/10.1038/s41541-021-00329-0 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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 |
spellingShingle |
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 npj Vaccines |
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 Publishing Group |
series |
npj Vaccines |
issn |
2059-0105 |
publishDate |
2021-05-01 |
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. |
url |
https://doi.org/10.1038/s41541-021-00329-0 |
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