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

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 propose...

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Bibliographic Details
Published innpj vaccines Vol. 8; no. 1; pp. 97 - 14
Main Authors Miller, Shannon M., Crouse, Bethany, Hicks, Linda, Amin, Hardik, Cole, Shelby, Bazin, Helene G., Burkhart, David J., Pravetoni, Marco, Evans, Jay T.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 10.07.2023
Nature Publishing Group
Nature Portfolio
Subjects
631/250/2152/2153/1291
631/250/262/2106/2108
631/250/590/1962
631/250/590/2291
692/699/476/5
Adjuvants
Antibodies
Biomedical and Life Sciences
Biomedicine
Cocaine
Drug overdose
Fentanyl
Heroin
Infectious Diseases
Medical Microbiology
Methadone
Narcotics
Pandemics
Prescription drugs
Public Health
Rodents
Substance use disorder
Vaccine
Vaccines
Virology
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Summary: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, F 1 , conjugated to the diphtheria cross-reactive material (CRM), significantly increased generation of high-affinity F 1 -specific antibody concentrations, and reduced drug distribution to the brain after fentanyl administration in mice.
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ISSN:2059-0105
2059-0105
DOI:10.1038/s41541-023-00694-y