Open AccessCombined TLR7/8 and TLR9 Ligands Potentiate the Activity of a Schistosoma japonicum DNA Vaccine
Author(s) -
Xuefeng Wang,
Liyang Dong,
Hemin Ni,
Sha Zhou,
Zhipeng Xu,
Jason S. Hoellwarth,
Xiaojun Chen,
Rongbo Zhang,
Qiaoyun Chen,
Feng Liu,
Jun Wang,
Chuan Su
Publication year - 2013
Publication title -
plos neglected tropical diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.99
H-Index - 135
eISSN - 1935-2735
pISSN - 1935-2727
DOI - 10.1371/journal.pntd.0002164
Subject(s) - schistosoma japonicum , tlr9 , tlr7 , schistosoma , virology , dna vaccination , biology , computational biology , dna , genetics , schistosoma mansoni , schistosomiasis , immunology , receptor , toll like receptor , gene , innate immune system , helminths , plasmid , gene expression , dna methylation
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.