2. Academic Validation
  3. A lipidated TLR7/8 adjuvant enhances the efficacy of a vaccine against fentanyl in mice

A lipidated TLR7/8 adjuvant enhances the efficacy of a vaccine against fentanyl in mice

  • NPJ Vaccines. 2023 Jul 10;8(1):97. doi: 10.1038/s41541-023-00694-y.
Shannon M Miller 1 2,  Bethany Crouse 3 4,  Linda Hicks 1,  Hardik Amin 1,  Shelby Cole 5,  Helene G Bazin 1 2,  David J Burkhart 1 2,  Marco Pravetoni 3 6 7,  Jay T Evans 8 9
Affiliations

Affiliations

  • 1 Department of Biomedical and Pharmaceutical Sciences, Center for Translational Medicine, University of Montana, Missoula, MT, USA.
  • 2 Inimmune Corporation, Missoula, MT, USA.
  • 3 Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN, USA.
  • 4 Department of Veterinary Population Medicine, University of Minnesota, St. Paul, MN, USA.
  • 5 Division of Biological Sciences, University of Montana, Missoula, MT, USA.
  • 6 Center for Immunology, University of Minnesota, Minneapolis, MN, USA.
  • 7 Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA.
  • 8 Department of Biomedical and Pharmaceutical Sciences, Center for Translational Medicine, University of Montana, Missoula, MT, USA. jay.evans@mso.umt.edu.
  • 9 Inimmune Corporation, Missoula, MT, USA. jay.evans@mso.umt.edu.
PMID: 37429853 DOI: 10.1038/s41541-023-00694-y
Abstract

Opioid use disorders (OUD) and opioid-related fatal overdoses are a public health concern in the United States. Approximately 100,000 fatal opioid-related overdoses occurred annually from mid-2020 to the present, the majority of which involved fentanyl or fentanyl analogs. Vaccines have been proposed as a therapeutic and prophylactic strategy to offer selective and long-lasting protection against accidental or deliberate exposure to fentanyl and closely related analogs. To support the development of a clinically viable anti-opioid vaccine suitable for human use, the incorporation of adjuvants will be required to elicit high titers of high-affinity circulating Antibodies specific to the target opioid. Here we demonstrate that the addition of a synthetic TLR7/8 agonist, INI-4001, but not a synthetic TLR4 Agonist, INI-2002, to a candidate conjugate vaccine consisting of a fentanyl-based Hapten, F1, conjugated to the diphtheria cross-reactive material (CRM), significantly increased generation of high-affinity F1-specific antibody concentrations, and reduced drug distribution to the brain after fentanyl administration in mice.

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