In this section
The Network aims to promote multi-disciplinary approaches to address challenging vaccine-related questions. This page contains a curated list of publications that highlight high-impact and collaborative approaches.
@article{Fischetti:2017:10.1016/j.cyto.2017.08.009,
author = {Fischetti, L and Zhong, Z and Pinder, CL and Tregoning, JS and Shattock, RJ},
doi = {10.1016/j.cyto.2017.08.009},
journal = {Cytokine},
pages = {287--296},
title = {The synergistic effects of combining TLR ligand based adjuvants on the cytokine response are dependent upon p38/JNK signalling.},
url = {http://dx.doi.org/10.1016/j.cyto.2017.08.009},
volume = {99},
year = {2017}
}
TY - JOUR
AB - Toll like receptor (TLR) ligands are important adjuvant candidates, causing antigen presenting cells to release inflammatory mediators, leading to the recruitment and activation of other leukocytes. The aim of this study was to define the response of human blood derived dendritic cells and macrophages to three TLR ligands acting singly or in combination, Poly I:C (TLR3), GLA (TLR4) and R848 (TLR7/8). Combinations of TLR agonists have been shown to have a synergistic effect on individual cytokines, here we look at the global inflammatory response measuring both cytokines and chemokines. Using a custom Luminex assay we saw dose responses in several mediators including CCL3 (MIP1α), IL-1α, IL-1β, IL-12, CXCL10 (IP-10) and IL-6, all of which were significantly increased by the combination of R848 and GLA, even when low dose GLA was added. The synergistic effect was inhibited by specific MAP kinase inhibitors blocking the kinases p38 and JNK but not MEK1. Combining TLR adjuvants also had a synergistic effect on cytokine responses in human mucosal tissue explants. From this we conclude that the combination of R848 and GLA potentiates the inflammatory profile of antigen presenting cells. Since the pattern of inflammatory mediators released can alter the quality and quantity of the adaptive immune response to vaccination, this study informs vaccine adjuvant design.
AU - Fischetti,L
AU - Zhong,Z
AU - Pinder,CL
AU - Tregoning,JS
AU - Shattock,RJ
DO - 10.1016/j.cyto.2017.08.009
EP - 296
PY - 2017///
SN - 1043-4666
SP - 287
TI - The synergistic effects of combining TLR ligand based adjuvants on the cytokine response are dependent upon p38/JNK signalling.
T2 - Cytokine
UR - http://dx.doi.org/10.1016/j.cyto.2017.08.009
UR - http://hdl.handle.net/10044/1/50406
VL - 99
ER -
Clinical Senior Lecturer
Dr Christopher Chiu
vaccine.network@imperial.ac.uk
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