A super TLR agonist to improve efficacy of dendritic cell vaccine in induction of anti-HCV immunity.

Persistent infections caused by pathogens such as hepatitis C virus are major human diseases with limited or suboptimal prophylactic and therapeutic options. Given the critical role of dendritic cell (DC) in inducing immune responses, DC vaccination is an attractive means to prevent and control the...

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Main Authors: Bangxing Hong, Sung-Hyung Lee, Xiao-Tong Song, Lindsey Jones, Keigo Machida, Xue F Huang, Si-Yi Chen
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3492467?pdf=render
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author Bangxing Hong
Sung-Hyung Lee
Xiao-Tong Song
Lindsey Jones
Keigo Machida
Xue F Huang
Si-Yi Chen
author_facet Bangxing Hong
Sung-Hyung Lee
Xiao-Tong Song
Lindsey Jones
Keigo Machida
Xue F Huang
Si-Yi Chen
author_sort Bangxing Hong
collection DOAJ
description Persistent infections caused by pathogens such as hepatitis C virus are major human diseases with limited or suboptimal prophylactic and therapeutic options. Given the critical role of dendritic cell (DC) in inducing immune responses, DC vaccination is an attractive means to prevent and control the occurrence and persistence of the infections. However, DCs are built-in with inherent negative regulation mechanisms which attenuate their immune stimulatory activity and lead to their ineffectiveness in clinical application. In this study, we developed a super DC stimulant that consists of a modified, secretory Toll-like Receptor (TLR)-5 ligand and an inhibitor of the negative regulator, suppressor of cytokine sinaling-1 (SOCS1). We found that expressing the super stimulant in DCs is drastically more potent and persistent than using the commonly used DC stimuli to enhance the level and duration of inflammatory cytokine production by both murine and human DCs. Moreover, the DCs expressing the super stimulant are more potent to provoke both cellular and humoral immune responses against hepatitis C virus (HCV) antigen in vivo. Thus, the strategy capable of triggering and sustaining proinflammatory status of DCs may be used to boost efficiency of DC vaccine in preventing and combating the persistent infection of HCV or other chronic viruses.
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spelling doaj.art-e0e9227705a944e890fb1a3f4e6b1f492022-12-21T22:26:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01711e4861410.1371/journal.pone.0048614A super TLR agonist to improve efficacy of dendritic cell vaccine in induction of anti-HCV immunity.Bangxing HongSung-Hyung LeeXiao-Tong SongLindsey JonesKeigo MachidaXue F HuangSi-Yi ChenPersistent infections caused by pathogens such as hepatitis C virus are major human diseases with limited or suboptimal prophylactic and therapeutic options. Given the critical role of dendritic cell (DC) in inducing immune responses, DC vaccination is an attractive means to prevent and control the occurrence and persistence of the infections. However, DCs are built-in with inherent negative regulation mechanisms which attenuate their immune stimulatory activity and lead to their ineffectiveness in clinical application. In this study, we developed a super DC stimulant that consists of a modified, secretory Toll-like Receptor (TLR)-5 ligand and an inhibitor of the negative regulator, suppressor of cytokine sinaling-1 (SOCS1). We found that expressing the super stimulant in DCs is drastically more potent and persistent than using the commonly used DC stimuli to enhance the level and duration of inflammatory cytokine production by both murine and human DCs. Moreover, the DCs expressing the super stimulant are more potent to provoke both cellular and humoral immune responses against hepatitis C virus (HCV) antigen in vivo. Thus, the strategy capable of triggering and sustaining proinflammatory status of DCs may be used to boost efficiency of DC vaccine in preventing and combating the persistent infection of HCV or other chronic viruses.http://europepmc.org/articles/PMC3492467?pdf=render
spellingShingle Bangxing Hong
Sung-Hyung Lee
Xiao-Tong Song
Lindsey Jones
Keigo Machida
Xue F Huang
Si-Yi Chen
A super TLR agonist to improve efficacy of dendritic cell vaccine in induction of anti-HCV immunity.
PLoS ONE
title A super TLR agonist to improve efficacy of dendritic cell vaccine in induction of anti-HCV immunity.
title_full A super TLR agonist to improve efficacy of dendritic cell vaccine in induction of anti-HCV immunity.
title_fullStr A super TLR agonist to improve efficacy of dendritic cell vaccine in induction of anti-HCV immunity.
title_full_unstemmed A super TLR agonist to improve efficacy of dendritic cell vaccine in induction of anti-HCV immunity.
title_short A super TLR agonist to improve efficacy of dendritic cell vaccine in induction of anti-HCV immunity.
title_sort super tlr agonist to improve efficacy of dendritic cell vaccine in induction of anti hcv immunity
url http://europepmc.org/articles/PMC3492467?pdf=render
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