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 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 13, 2021
- Source ID
- 10.1038/s41541-021-00329-0
Entities
People
- Addison E. Stone
- Anantha L Duddupudi
- Colin N. Haile
- Elizabeth B Norton
- Gregory D Cuny
- Jennifer R. Vigliaturo
- Joshua P. Linhuber
- Marcela Lopez Velasquez
- Marco Pravetoni
- Sarah E. Scheuermann
- Therese A. Kosten
- Thomas R Kosten
Organizations
- National Institute of Allergy and Infectious Diseases
- United States Department of Defense
- United States Department of Health and Human Services