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

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

doi:10.1038/s41541-021-00329-0

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

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

Pharmacology

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19 Scopus citations

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.

Original language	English (US)
Article number	69
Journal	npj Vaccines
Volume	6
Issue number	1
DOIs	https://doi.org/10.1038/s41541-021-00329-0
State	Published - Dec 2021

Bibliographical note

Funding Information:
Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number R01AI114697 and the Department of Defense USAMRAA, W81-XWH-15-2-007. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors want to thank Sergio Sanchez and Miah Baker for technical assistance and Amelie Murrell for literature review.

Publisher Copyright:
© 2021, The Author(s).

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Stone, A. E., Scheuermann, S. E., Haile, C. N., Cuny, G. D., Velasquez, M. L., Linhuber, J. P., Duddupudi, A. L., Vigliaturo, J. R., Pravetoni, M., Kosten, T. A., Kosten, T. R., & Norton, E. B. (2021). Fentanyl conjugate vaccine by injected or mucosal delivery with dmLT or LTA1 adjuvants implicates IgA in protection from drug challenge. npj Vaccines, 6(1), Article 69. https://doi.org/10.1038/s41541-021-00329-0

Stone, AE, Scheuermann, SE, Haile, CN, Cuny, GD, Velasquez, ML, Linhuber, JP, Duddupudi, AL, Vigliaturo, JR, Pravetoni, M, Kosten, TA, Kosten, TR & Norton, EB 2021, 'Fentanyl conjugate vaccine by injected or mucosal delivery with dmLT or LTA1 adjuvants implicates IgA in protection from drug challenge', npj Vaccines, vol. 6, no. 1, 69. https://doi.org/10.1038/s41541-021-00329-0

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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.",

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AU - Cuny, Gregory D.

AU - Velasquez, Marcela Lopez

AU - Linhuber, Joshua P.

AU - Duddupudi, Anantha L.

AU - Vigliaturo, Jennifer R.

AU - Pravetoni, Marco

AU - Kosten, Therese A.

AU - Kosten, Thomas R.

AU - Norton, Elizabeth B.

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

Abstract

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