title: Combined TLR7/8 and TLR9 ligands potentiate the activity of a Schistosoma japonicum DNA vaccine.
abstract: 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).
  
  
  RESULTS
  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.
authors.affiliation: Department of Central Laboratory, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China. wangxxff1023@yahoo.com.cn
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wang
authors.forename: Liyang
authors.initials: L
authors.lastname: Dong
authors.forename: Hongchang
authors.initials: H
authors.lastname: Ni
authors.forename: Sha
authors.initials: S
authors.lastname: Zhou
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Xu
authors.forename: Jason Shih
authors.initials: JS
authors.lastname: Hoellwarth
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Chen
authors.forename: Rongbo
authors.initials: R
authors.lastname: Zhang
authors.forename: Qiaoyun
authors.initials: Q
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Chuan
authors.initials: C
authors.lastname: Su
mesh_terms: D000818:Animals; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism; D015801:Helminth Proteins / Q000819:agonists / Q000235:genetics; D007093:Imidazoles / Q000627:therapeutic use*; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use*; D016052:Protozoan Vaccines / Q000627:therapeutic use*; D012549:Schistosoma japonicum / Q000276:immunology* / Q000378:metabolism* / Q000472:pathogenicity; D012552:Schistosomiasis / Q000188:drug therapy* / Q000628:therapy*; D013154:Spleen / Q000166:cytology; D051199:Toll-Like Receptor 7 / Q000819:agonists / Q000378:metabolism*; D051200:Toll-Like Receptor 8 / Q000819:agonists / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000378:metabolism; D019444:Vaccines, DNA / Q000627:therapeutic use*
chemical_list: D015801:Helminth Proteins; D007093:Imidazoles; D009838:Oligodeoxyribonucleotides; D016052:Protozoan Vaccines; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051217:Toll-Like Receptor 9; D019444:Vaccines, DNA; D005982:Glutathione Transferase; C402365:resiquimod