Combined TLR7/8 and TLR9 ligands potentiate the activity of a Schistosoma japonicum DNA vaccine.
BACKGROUND: Toll-like receptor (TLR) ligands have been explored as vaccine adjuvants for tumor and virus immunotherapy, but few TLR ligands affecting schistosoma vaccines have been characterized. Previously, we developed a partially protective DNA vaccine encoding the 26-kDa glutathione S-transferas...
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doaj-32af16568aac46cfa6a1e8801ed97bd92020-11-24T21:56:57ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352013-01-0174e216410.1371/journal.pntd.0002164Combined TLR7/8 and TLR9 ligands potentiate the activity of a Schistosoma japonicum DNA vaccine.Xuefeng WangLiyang DongHongchang NiSha ZhouZhipeng XuJason Shih HoellwarthXiaojun ChenRongbo ZhangQiaoyun ChenFeng LiuJun WangChuan SuBACKGROUND: Toll-like receptor (TLR) ligands have been explored as vaccine adjuvants for tumor and virus immunotherapy, but few TLR ligands affecting schistosoma vaccines have been characterized. Previously, we developed a partially protective DNA vaccine encoding the 26-kDa glutathione S-transferase of Schistosoma japonicum (pVAX1-Sj26GST). METHODOLOGY/PRINCIPAL FINDINGS: In this study, we evaluated a TLR7/8 ligand (R848) and a TLR9 ligand (CpG oligodeoxynucleotides, or CpG) as adjuvants for pVAX1-Sj26GST and assessed their effects on the immune system and protection against S. japonicum. We show that combining CpG and R848 with pVAX1-Sj26GST immunization significantly increases splenocyte proliferation and IgG and IgG2a levels, decreases CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) frequency in vivo, and enhances protection against S. japonicum. CpG and R848 inhibited Treg-mediated immunosuppression, upregulated the production of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-10, IL-2, and IL-6, and decreased Foxp3 expression in vitro, which may contribute to prevent Treg suppression and conversion during vaccination and allow expansion of antigen-specific T cells against pathogens. CONCLUSIONS: Our data shows that selective TLR ligands can increase the protective efficacy of DNA vaccines against schistosomiasis, potentially through combined antagonism of Treg-mediated immunosuppression and conversion.http://europepmc.org/articles/PMC3617091?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xuefeng Wang Liyang Dong Hongchang Ni Sha Zhou Zhipeng Xu Jason Shih Hoellwarth Xiaojun Chen Rongbo Zhang Qiaoyun Chen Feng Liu Jun Wang Chuan Su |
spellingShingle |
Xuefeng Wang Liyang Dong Hongchang Ni Sha Zhou Zhipeng Xu Jason Shih Hoellwarth Xiaojun Chen Rongbo Zhang Qiaoyun Chen Feng Liu Jun Wang Chuan Su Combined TLR7/8 and TLR9 ligands potentiate the activity of a Schistosoma japonicum DNA vaccine. PLoS Neglected Tropical Diseases |
author_facet |
Xuefeng Wang Liyang Dong Hongchang Ni Sha Zhou Zhipeng Xu Jason Shih Hoellwarth Xiaojun Chen Rongbo Zhang Qiaoyun Chen Feng Liu Jun Wang Chuan Su |
author_sort |
Xuefeng Wang |
title |
Combined TLR7/8 and TLR9 ligands potentiate the activity of a Schistosoma japonicum DNA vaccine. |
title_short |
Combined TLR7/8 and TLR9 ligands potentiate the activity of a Schistosoma japonicum DNA vaccine. |
title_full |
Combined TLR7/8 and TLR9 ligands potentiate the activity of a Schistosoma japonicum DNA vaccine. |
title_fullStr |
Combined TLR7/8 and TLR9 ligands potentiate the activity of a Schistosoma japonicum DNA vaccine. |
title_full_unstemmed |
Combined TLR7/8 and TLR9 ligands potentiate the activity of a Schistosoma japonicum DNA vaccine. |
title_sort |
combined tlr7/8 and tlr9 ligands potentiate the activity of a schistosoma japonicum dna vaccine. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Neglected Tropical Diseases |
issn |
1935-2727 1935-2735 |
publishDate |
2013-01-01 |
description |
BACKGROUND: Toll-like receptor (TLR) ligands have been explored as vaccine adjuvants for tumor and virus immunotherapy, but few TLR ligands affecting schistosoma vaccines have been characterized. Previously, we developed a partially protective DNA vaccine encoding the 26-kDa glutathione S-transferase of Schistosoma japonicum (pVAX1-Sj26GST). METHODOLOGY/PRINCIPAL FINDINGS: In this study, we evaluated a TLR7/8 ligand (R848) and a TLR9 ligand (CpG oligodeoxynucleotides, or CpG) as adjuvants for pVAX1-Sj26GST and assessed their effects on the immune system and protection against S. japonicum. We show that combining CpG and R848 with pVAX1-Sj26GST immunization significantly increases splenocyte proliferation and IgG and IgG2a levels, decreases CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) frequency in vivo, and enhances protection against S. japonicum. CpG and R848 inhibited Treg-mediated immunosuppression, upregulated the production of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-10, IL-2, and IL-6, and decreased Foxp3 expression in vitro, which may contribute to prevent Treg suppression and conversion during vaccination and allow expansion of antigen-specific T cells against pathogens. CONCLUSIONS: Our data shows that selective TLR ligands can increase the protective efficacy of DNA vaccines against schistosomiasis, potentially through combined antagonism of Treg-mediated immunosuppression and conversion. |
url |
http://europepmc.org/articles/PMC3617091?pdf=render |
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