Cutting Edge: A Dual TLR2 and TLR7 Ligand Induces Highly Potent Humoral and Cell-Mediated Immune Responses

J Immunol. 2017 Jun 1;198(11):4205-4209. doi: 10.4049/jimmunol.1602131. Epub 2017 Apr 21.

Abstract

TLR agonists are currently being developed and tested as adjuvants in various formulations to optimize the immunogenicity and efficacy of vaccines. The aim of this study was to evaluate the immunostimulatory properties of a novel compound incorporating covalently linked moieties designed to stimulate both TLR2 and TLR7. This dual TLR2/TLR7 agonist induced the maturation of dendritic cells and primed substantial populations of cytolytic and highly polyfunctional effector CD8+ T cells in vitro, and safely potentiated the immunogenic properties of a nanoparticulate Ag in vivo, eliciting humoral responses with a balanced TH1/TH2 profile in mice. Collectively, these data reveal the potential utility of chimeric adjuvants with synergistic activities mediated via TLRs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic*
  • Animals
  • Antibody Formation
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation
  • Cytokines
  • Dendritic Cells / immunology
  • Dendritic Cells / physiology
  • HIV Core Protein p24 / administration & dosage
  • HIV Core Protein p24 / immunology
  • Immunity, Cellular*
  • Immunity, Humoral*
  • Ligands
  • Membrane Glycoproteins / agonists*
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles
  • Recombinant Fusion Proteins / immunology
  • Toll-Like Receptor 2 / agonists*
  • Toll-Like Receptor 2 / immunology*
  • Toll-Like Receptor 7 / agonists*
  • Toll-Like Receptor 7 / immunology*
  • Vaccination

Substances

  • Adjuvants, Immunologic
  • Cytokines
  • HIV Core Protein p24
  • Ligands
  • Membrane Glycoproteins
  • Recombinant Fusion Proteins
  • Tlr2 protein, mouse
  • Tlr7 protein, mouse
  • Toll-Like Receptor 2
  • Toll-Like Receptor 7