Dual Synthetic Peptide Conjugate Vaccine Simultaneously Triggers TLR2 and NOD2 and Activates Human Dendritic Cells.

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Dual Synthetic Peptide Conjugate Vaccine Simultaneously Triggers TLR2 and NOD2 and Activates Human Dendritic Cells.

Type: Article / Letter to editor
Title: Dual Synthetic Peptide Conjugate Vaccine Simultaneously Triggers TLR2 and NOD2 and Activates Human Dendritic Cells.
Author: Zom, G.G.Willems, M.M.J.H.P.Meeuwenoord, N.Reintjens, N.R.M.Tondini, E.Khan, S.Overkleeft, H.S.Marel, G.A. van derCodée, J.D.C.Ossendorp, F.Filippov, D.V.
Journal Title: Bioconjugate Chemistry
Issue: 4
Volume: 30
Start Page: 1150
End Page: 1161
Pages: 12
Issue Date: 2019
Abstract: 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.
Uri: https://pubs.acs.org/doi/10.1021/acs.bioconjchem.9b00087
Handle: http://hdl.handle.net/1887/72253
 

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