Dual Synthetic Peptide Conjugate Vaccine Simultaneously Triggers TLR2 and NOD2 and Activates Human Dendritic Cells.
Gijs G ZomMarian M J H P WillemsNico J MeeuwenoordNiels R M ReintjensElena TondiniSelina KhanHerman S OverkleeftGijsbert A van der MarelJeroen D C CodéeFerry OssendorpDmitri V FilippovPublished in: Bioconjugate chemistry (2019)
Simultaneous triggering of Toll-like receptors (TLRs) and NOD-like receptors (NLRs) has previously been shown to synergistically activate monocytes, dendritic cells, and macrophages. We applied these properties in a T-cell vaccine setting by conjugating the NOD2-ligand muramyl-dipeptide (MDP) and TLR2-ligand Pam3CSK4 to a synthetic peptide derived from a model antigen. Stimulation of human DCs with the MDP-peptide-Pam3CSK4 conjugate led to a strongly increased secretion of pro-inflammatory and Th1-type cytokines and chemokines. We further show that the conjugated ligands retain their ability to trigger their respective receptors, while even improving NOD2-triggering. Also, activation of murine DCs was enhanced by the dual triggering, ultimately leading to effective induction of vaccine-specific T cells expressing IFNγ, IL-2, and TNFα. Together, these data indicate that the dual MDP-SLP-Pam3CSK4 conjugate constitutes a chemically well-defined vaccine approach that holds promise for the use in the treatment of virus infections and cancer.
Keyphrases
- dendritic cells
- immune response
- endothelial cells
- toll like receptor
- regulatory t cells
- inflammatory response
- innate immune
- cancer therapy
- rheumatoid arthritis
- induced pluripotent stem cells
- big data
- pluripotent stem cells
- photodynamic therapy
- squamous cell carcinoma
- papillary thyroid
- drug delivery
- replacement therapy