A f entanyl hapten-displaying lipid nanoparticle vaccine that non-covalently encapsulates a TLR7/8 agonist and T-helper epitope induces protective anti-fentanyl immunity
- Author
- Zifu Zhong (UGent) , Marie Deventer (UGent) , Yong Chen (UGent) , Stijn Vanhee (UGent) , Inés Lammens (UGent) , Kim Deswarte (UGent) , Yi Huang (UGent) , Tingting Ye (UGent) , Haixiu Wang (UGent) , Lutz Nuhn, Marthe Vandeputte (UGent) , Mark Gontsarik (UGent) , Xiaole Cui (UGent) , Niek Sanders (UGent) , Stefan Lienenklaus, Bart Lambrecht (UGent) , Antonio Pires da Silva Baptista (UGent) , Christophe Stove (UGent) and Bruno De Geest (UGent)
- Organization
- Project
-
- Non-covalent hapten-immunogen next generation anti-opioid nanovaccines
- ImmunoBioSynth (Synergistic engineering of anti-tumor immunity by synthetic biomaterials)
- Making sense of screening for new psychoactive substances: Towards on-site receptor-based sensing of synthetic cannabinoids and opioids.
- Abstract
- Opioid use disorder - particularly involving fentanyl - has precipitated a public health crisis characterized by a significant increase in addiction and overdose-related deaths. Fentanyl-specific immunotherapy, which aims at inducing fentanyl-specific antibodies capable of binding fentanyl molecules in the bloodstream, preventing their entry in the central nervous system, is therefore gaining momentum. Conventional opioid designs rely on the covalent conjugation of fentanyl analogues to immunogenic carrier proteins that hold the inherent capacity of mounting immunodominant responses. Here, we present an alternative fentanyl vaccine design that utilizes a non-covalent assembly of lipid nanoparticles (LNPs) to deliver fentanyl haptens in conjunction with a CD4+ T-helper peptide epitope and an imidazoquinoline TLR7/8 agonist. Our results demonstrate that a single intramuscular administration of the LNP-based nanovaccine elicits fentanyl-specific antibodies, significantly mitigating the effects of opioid overdose in preclinical mouse models. Furthermore, we analyzed the immunobiological behavior of the vaccine in vivo in mouse models, providing evidence that covalent attachment of a fentanyl hapten to a carrier proteins or peptide epitope is not necessary for inducing an effective immune response. However, co-delivery - specifically, the physical assembly of all immune cues into an LNP - remains essential for inducing hapten-specific immunity.
- Keywords
- fentanyl vaccine, lipid nanoparticle, hapten, imidazoquinolines, peptide, HEROIN, IMIDAZOQUINOLINE, SUPPRESSION, PARTICLES, INDUCTION, RESPONSES
Downloads
-
AAM-Zhong Deventer Fentanyl vaccine MS.docx
- full text (Accepted manuscript)
- |
- open access
- |
- Word
- |
- 7.81 MB
Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01JPJ27D3SCDYF0DTY61Q19XZW
- MLA
- Zhong, Zifu, et al. “A f Entanyl Hapten-Displaying Lipid Nanoparticle Vaccine That Non-Covalently Encapsulates a TLR7/8 Agonist and T-Helper Epitope Induces Protective Anti-Fentanyl Immunity.” ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, vol. 64, no. 7, 2025, doi:10.1002/anie.202419031.
- APA
- Zhong, Z., Deventer, M., Chen, Y., Vanhee, S., Lammens, I., Deswarte, K., … De Geest, B. (2025). A f entanyl hapten-displaying lipid nanoparticle vaccine that non-covalently encapsulates a TLR7/8 agonist and T-helper epitope induces protective anti-fentanyl immunity. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 64(7). https://doi.org/10.1002/anie.202419031
- Chicago author-date
- Zhong, Zifu, Marie Deventer, Yong Chen, Stijn Vanhee, Inés Lammens, Kim Deswarte, Yi Huang, et al. 2025. “A f Entanyl Hapten-Displaying Lipid Nanoparticle Vaccine That Non-Covalently Encapsulates a TLR7/8 Agonist and T-Helper Epitope Induces Protective Anti-Fentanyl Immunity.” ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 64 (7). https://doi.org/10.1002/anie.202419031.
- Chicago author-date (all authors)
- Zhong, Zifu, Marie Deventer, Yong Chen, Stijn Vanhee, Inés Lammens, Kim Deswarte, Yi Huang, Tingting Ye, Haixiu Wang, Lutz Nuhn, Marthe Vandeputte, Mark Gontsarik, Xiaole Cui, Niek Sanders, Stefan Lienenklaus, Bart Lambrecht, Antonio Pires da Silva Baptista, Christophe Stove, and Bruno De Geest. 2025. “A f Entanyl Hapten-Displaying Lipid Nanoparticle Vaccine That Non-Covalently Encapsulates a TLR7/8 Agonist and T-Helper Epitope Induces Protective Anti-Fentanyl Immunity.” ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 64 (7). doi:10.1002/anie.202419031.
- Vancouver
- 1.Zhong Z, Deventer M, Chen Y, Vanhee S, Lammens I, Deswarte K, et al. A f entanyl hapten-displaying lipid nanoparticle vaccine that non-covalently encapsulates a TLR7/8 agonist and T-helper epitope induces protective anti-fentanyl immunity. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION. 2025;64(7).
- IEEE
- [1]Z. Zhong et al., “A f entanyl hapten-displaying lipid nanoparticle vaccine that non-covalently encapsulates a TLR7/8 agonist and T-helper epitope induces protective anti-fentanyl immunity,” ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, vol. 64, no. 7, 2025.
@article{01JPJ27D3SCDYF0DTY61Q19XZW,
abstract = {{Opioid use disorder - particularly involving fentanyl - has precipitated a public health crisis characterized by a significant increase in addiction and overdose-related deaths. Fentanyl-specific immunotherapy, which aims at inducing fentanyl-specific antibodies capable of binding fentanyl molecules in the bloodstream, preventing their entry in the central nervous system, is therefore gaining momentum. Conventional opioid designs rely on the covalent conjugation of fentanyl analogues to immunogenic carrier proteins that hold the inherent capacity of mounting immunodominant responses. Here, we present an alternative fentanyl vaccine design that utilizes a non-covalent assembly of lipid nanoparticles (LNPs) to deliver fentanyl haptens in conjunction with a CD4+ T-helper peptide epitope and an imidazoquinoline TLR7/8 agonist. Our results demonstrate that a single intramuscular administration of the LNP-based nanovaccine elicits fentanyl-specific antibodies, significantly mitigating the effects of opioid overdose in preclinical mouse models. Furthermore, we analyzed the immunobiological behavior of the vaccine in vivo in mouse models, providing evidence that covalent attachment of a fentanyl hapten to a carrier proteins or peptide epitope is not necessary for inducing an effective immune response. However, co-delivery - specifically, the physical assembly of all immune cues into an LNP - remains essential for inducing hapten-specific immunity.}},
articleno = {{e202419031}},
author = {{Zhong, Zifu and Deventer, Marie and Chen, Yong and Vanhee, Stijn and Lammens, Inés and Deswarte, Kim and Huang, Yi and Ye, Tingting and Wang, Haixiu and Nuhn, Lutz and Vandeputte, Marthe and Gontsarik, Mark and Cui, Xiaole and Sanders, Niek and Lienenklaus, Stefan and Lambrecht, Bart and Pires da Silva Baptista, Antonio and Stove, Christophe and De Geest, Bruno}},
issn = {{1433-7851}},
journal = {{ANGEWANDTE CHEMIE-INTERNATIONAL EDITION}},
keywords = {{fentanyl vaccine,lipid nanoparticle,hapten,imidazoquinolines,peptide,HEROIN,IMIDAZOQUINOLINE,SUPPRESSION,PARTICLES,INDUCTION,RESPONSES}},
language = {{eng}},
number = {{7}},
pages = {{12}},
title = {{A f entanyl hapten-displaying lipid nanoparticle vaccine that non-covalently encapsulates a TLR7/8 agonist and T-helper epitope induces protective anti-fentanyl immunity}},
url = {{http://doi.org/10.1002/anie.202419031}},
volume = {{64}},
year = {{2025}},
}
- Altmetric
- View in Altmetric
- Web of Science
- Times cited: