Activation of monocytic cells by immunostimulatory lipids conjugated to peptide antigens

Mol Biosyst. 2012 Oct 30;8(12):3166-77. doi: 10.1039/c2mb25064k.

Abstract

Bacterial derived lipoproteins constitute potent macrophage activators in vivo and are effective stimuli, enhancing the immune response especially with respect to low or non-immunogenic compounds. In the present study we have prepared branched lipopeptide constructs in which different (B- and T-cell) epitopes of Herpes simplex virus type 1, derived from glycoproteins B (gB) and D (gD), are linked to a synthetic lipid core. The ability of the lipid core peptide (LCP) constructs (LCP-gB and LCP-gD) to induce cytokine expression and activate the mitogen-activated protein kinase cascade has been evaluated and compared with the behaviour of the isolated epitopes and the lipid core. In this respect, the use of LCP technology coupled with the use of three different gB or gD peptide epitopes in the same branched constructs could represent an interesting approach in order to obtain efficient delivery systems in the development of a synthetic multiepitopic vaccine for the prevention of viral infections.

MeSH terms

  • Animals
  • Antigens, Bacterial / chemistry
  • Antigens, Bacterial / immunology
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Cell Line, Tumor
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Enzyme Inhibitors / pharmacology
  • Epitopes, B-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / immunology
  • Flavonoids / pharmacology
  • Herpesvirus 1, Human / immunology
  • Humans
  • Imidazoles / pharmacology
  • Immunization*
  • Lipid Metabolism
  • Lipids / immunology*
  • Macrophage Activation
  • Macrophages / immunology*
  • Mice
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / immunology
  • Monocytes / immunology*
  • Peptides / immunology*
  • Peptides / metabolism
  • Peptides / pharmacology
  • Pyridines / pharmacology
  • Viral Envelope Proteins / immunology
  • Viral Envelope Proteins / metabolism

Substances

  • Antigens, Bacterial
  • Cytokines
  • Enzyme Inhibitors
  • Epitopes, B-Lymphocyte
  • Epitopes, T-Lymphocyte
  • Flavonoids
  • Imidazoles
  • L-JNKI-1
  • Lipids
  • Peptides
  • Pyridines
  • Viral Envelope Proteins
  • glycoprotein B, human herpesvirus 1
  • glycoprotein D, Human herpesvirus 1
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases
  • SB 203580
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one