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Scientific article
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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

Published inFrontiers in immunology, vol. 11, 580974
Publication date2020
First online date2020-11-11
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 (TH) 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 TH1 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 TH1 and germinal center responses.

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Keywords
  • TLR7/8 agonist
  • Adjuvants for vaccine
  • Follicular T helper cells
  • Germinal centers
  • Liposome
  • 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
Citation (ISO format)
AUDERSET, Floriane et al. 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. In: Frontiers in immunology, 2020, vol. 11, p. 580974. doi: 10.3389/fimmu.2020.580974
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Article (Published version)
Identifiers
ISSN of the journal1664-3224
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