A TLR7/8 Agonist-Including DOEPC-Based Cationic Liposome Formulation Mediates Its Adjuvanticity Through the Sustained Recruitment of Highly Activated Monocytes in a Type I IFN-Independent but NF-κB-Dependent Manner.

Details

Serval ID
serval:BIB_B3824234F961
Type
Article: article from journal or magazin.
Collection
Publications
Title
A TLR7/8 Agonist-Including DOEPC-Based Cationic Liposome Formulation Mediates Its Adjuvanticity Through the Sustained Recruitment of Highly Activated Monocytes in a Type I IFN-Independent but NF-κB-Dependent Manner.
Journal
Frontiers in immunology
Author(s)
Auderset F., Belnoue E., Mastelic-Gavillet B., Lambert P.H., Siegrist C.A.
ISSN
1664-3224 (Electronic)
ISSN-L
1664-3224
Publication state
Published
Issued date
2020
Peer-reviewed
Oui
Volume
11
Pages
580974
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Novel adjuvants, such as Toll-like receptors (TLRs) agonists, are needed for the development of new formulations able to circumvent limitations of current vaccines. Among TLRs, TLR7/8 agonists represent promising candidates, as they are well described to enhance antigen-specific antibody responses and skew immunity toward T helper (T <sub>H</sub> ) 1 responses. We find here that the incorporation of the synthetic TLR7/8 ligand 3M-052 in a cationic DOEPC-based liposome formulation shifts immunity toward T <sub>H</sub> 1 responses and elicits strong and long-lasting germinal center and follicular T helper cell responses in adult mice. This reflects the prolonged recruitment of innate cells toward the site of immunization and homing of activated antigen-loaded monocytes and monocyte-derived dendritic cells toward draining lymph nodes. We further show that this adjuvanticity is independent of type I IFN but NF-κB-dependent. Overall, our data identify TLR7/8 agonists incorporated in liposomes as promising and effective adjuvants to enhance T <sub>H</sub> 1 and germinal center responses.
Keywords
Adjuvants, Immunologic/administration & dosage, Animals, B-Lymphocytes/immunology, Dendritic Cells/immunology, Drug Compounding, Germinal Center/immunology, Heterocyclic Compounds, 3-Ring/administration & dosage, Immunity, Innate, Interferon Type I/immunology, Ligands, Liposomes/administration & dosage, Membrane Glycoproteins/agonists, Mice, Mice, Inbred C57BL, Mice, Knockout, Monocytes/immunology, NF-kappa B/deficiency, NF-kappa B/genetics, NF-kappa B/immunology, Phosphatidylcholines/administration & dosage, Receptor, Interferon alpha-beta/deficiency, Receptor, Interferon alpha-beta/genetics, Receptor, Interferon alpha-beta/immunology, Signal Transduction/immunology, Stearic Acids/administration & dosage, Th1 Cells/immunology, Toll-Like Receptor 7/agonists, Toll-Like Receptor 8/agonists, TLR7/8 agonist, adjuvants for vaccine, follicular T helper cells, germinal centers, liposome
Pubmed
Web of science
Open Access
Yes
Create date
15/12/2020 9:06
Last modification date
23/02/2024 17:14
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