Synthetic triacylated lipid A derivative activates antigen presenting cells via the TLR4 pathway and promotes antigen-specific responses in vivo.
Triggering the maturation of dendritic cells (DC) with toll-like receptor (TLR) agonists is a favored strategy for the development of vaccine adjuvants. The triacyl pseudo-dipeptidic agent OM-197-MP-AC mimicking the lipid A structure of endotoxin induces the maturation of human monocyte-derived DC. In this study we investigated the signaling pathway by which this molecule activates DC. The ability of OM-197-MP-AC to induce maturation of human and mouse DC and macrophages was dependent on TLR4, not TLR2. Ovalbumin-specific humoral and T helper cell responses were significantly augmented by OM-197-MP-AC treatment. Taken together these results indicate that OM-197-MP-AC is a TLR4 agonist inducing DC maturation and represents a novel class of vaccine adjuvants devoid of the known pyrogenic effects associated with classical LPS derivatives.
Savoy
Fabienne
F
OM PHARMA, 22 rue du Bois-du-Lan, CH-1217 Meyrin/2, Switzerland.
Nicolle
Delphine M
DM
Rivier
Denis
D
Chiavaroli
Carlo
C
Ryffel
Bernhard
B
Quesniaux
Valérie F J
VF
D000215:Acylation; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D008050:Lipid A / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010743:Phospholipids / Q000276:immunology*; D015398:Signal Transduction / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000502:physiology*
D000939:Epitopes; D008050:Lipid A; C479638:OM 197-MP-AC; D010743:Phospholipids; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4