biostudies-literatureMiller SMU.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious DiseasesU.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse97https://www.ebi.ac.uk/biostudies/studies/S-EPMC10333387biostudies-literatureUnknown8(1)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.NPJ vaccinesA lipidated TLR7/8 adjuvant enhances the efficacy of a vaccine against fentanyl in mice.PMC10333387HHSN272201800048C75N93019R00009UG3DA048386Miller SMHicks LAmin HBurkhart DJCole SCrouse BBazin HGEvans JTPravetoni MfalseA 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 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.2023-01-01T00:00:00Z2023 Jul2024-11-21T05:20:20.591Z2024-11-21T05:20:20.591ZS-EPMC103333873742985310.1038/s41541-023-00694-y