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CpG oligodeoxynucleotide ligand potentiates the activity of the pVAX1-Sj26GST
Jun Lu1, Shan Jiang2, Song Ye1
1Department of Pathogen Biology and Immunology, School of Medicine, Anhui University of Science and Technology, P.R. China.
Abstract:
Schistosomiasis is considered one of the most important neglected tropical diseases and remains a major public health problem in endemic countries. Toll-like receptor (TLR) ligands have been investigated as potential vaccine adjuvants for tumor and virus immunotherapy. However, few TLR ligands affecting schistosoma vaccines have been characterized. In this study, we evaluated a TLR9 ligand (CpG oligodeoxynucleotide 1826, CpG) as an adjuvant for a partially protective DNA vaccine encoding a 26-kDa glutathione S-transferase of Schistosoma japonicum (pVAX1-Sj26GST). Vaccination with pVAX1-Sj26GST in combination with CpG inhibited Treg immunosuppressive function, upregulated the production of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-10, IL-2 and IL-6, and decreased CD4+CD8+Foxp3+ expression in vitro, which may contribute to the escape from Treg-mediated suppression during vaccination, allowing expansion of antigen-specific T cells against pathogens. In conclusion, our data demonstrated that selective TLR ligand combination may increase protective efficacy against schistosomiasis, which may synergistically antagonize Treg-mediated suppression.
Insights
This study explored Toll-like receptor 9 ligand (CpG) as an adjuvant for a Schistosoma japonicum vaccine. Combining CpG with the DNA vaccine enhanced immune responses and showed potential for improved schistosomiasis vaccine efficacy.
Area of Science:
- Immunology
- Parasitology
- Vaccinology
Background:
- Schistosomiasis is a major neglected tropical disease.
- Toll-like receptor (TLR) ligands are explored as vaccine adjuvants.
- Limited characterization of TLR ligands for schistosoma vaccines exists.
Purpose of the Study:
- To evaluate a TLR9 ligand (CpG) as an adjuvant for a Schistosoma japonicum DNA vaccine (pVAX1-Sj26GST).
- To investigate the adjuvant's effect on immune responses and regulatory T cell (Treg) function.
Main Methods:
- Vaccination with pVAX1-Sj26GST DNA vaccine and CpG adjuvant.
- In vitro assessment of Treg immunosuppressive function.
- Measurement of cytokine production (IFN-γ, TNF-α, IL-4, IL-10, IL-2, IL-6) and immune cell expression (CD4+CD8+Foxp3+).
Main Results:
- CpG adjuvant inhibited Treg immunosuppressive function.
- Upregulation of key cytokines including IFN-γ, TNF-α, and IL-4.
- Decreased CD4+CD8+Foxp3+ expression, suggesting reduced Treg activity.
- Potential for enhanced antigen-specific T cell expansion.
Conclusions:
- CpG acts as an effective adjuvant for the S. japonicum DNA vaccine.
- The combination therapy may overcome Treg-mediated suppression.
- Selective TLR ligand combinations show promise for increasing protective efficacy against schistosomiasis.
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