“…The glucopyranosyl lipid A (GLA) formulated in aluminum (GLA-Alum), a TLR4 ligand, combined with sm-p80 vaccine could induce balanced Th (Th1, Th2 and Th17) immune responses and significant sm-p80specific antibodies production in vaccinated animals but did not maximize the immunogenicity and efficacity of the vaccine as expected (Zhang et al, 2018). Investigation on the ligands of TLR7/8 (R848) and TLR9 (CpG oligonucleotide) revealed that both of them block Treg immunosuppressive function and upregulate the production of TNF-a, IFN-g, and several interleukins in vitro (Lu et al, 2013;Wang et al, 2013). Interestingly, in vivo experiment revealed that the combination of R848 and CpG with the DNA vaccine 26-kDa glutathione Stransferase of S. japonicum (pVAX1-Sj26GST) induces a significant protective immunity in animal model, suggesting that the combination of multiple TLR ligands may be targeted as a promising new approach for the design of Schistosoma vaccines (Wang et al, 2012;Wang et al, 2013).…”