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

Front Immunol. 2020 Nov 11:11:580974. doi: 10.3389/fimmu.2020.580974. eCollection 2020.

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.

Keywords: TLR7/8 agonist; adjuvants for vaccine; follicular T helper cells; germinal centers; liposome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

  • Adjuvants, Immunologic
  • Heterocyclic Compounds, 3-Ring
  • Ifnar1 protein, mouse
  • Interferon Type I
  • Ligands
  • Liposomes
  • Membrane Glycoproteins
  • NF-kappa B
  • Phosphatidylcholines
  • Stearic Acids
  • TLR8 protein, mouse
  • Tlr7 protein, mouse
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
  • Receptor, Interferon alpha-beta
  • MEDI9197
  • 1,2-oleoylphosphatidylcholine