State Key Laboratory for Agro-Biotechnology, Department of Microbiology and Immunology, College of Biological Science, China Agricultural University, Beijing 100193, China.
Vaccine. 2010 Feb 23;28(8):2032-8. doi: 10.1016/j.vaccine.2009.10.101.
Praziquantel (PZQ), which is used to treat all forms of schistosomiasis, has been shown to induce strong T cell activities and decrease T regulatory cell levels. In our study, we investigated whether PZQ may be used as an adjuvant for a hepatitis B surface antigen (HBsAg) DNA vaccine (pcD-S2) in eliciting strong humoral and cellular responses. Our data demonstrate that PZQ as an adjuvant increased T cell proliferation and an HBsAg-specific antibody response that was characterized by a higher ratio of IgG2a/IgG1. Moreover, a higher level of IFN-gamma in CD4(+) and CD8(+) T cells were elicited. In addition, a significantly antigen-specific cytotoxic T lymphocyte response was also observed. The expression of TGF-beta can be induced by HBsAg, while PZQ as an adjuvant can inhibit the expression of TGF-beta and TGF-beta/Smad2,3 signaling. The frequency of CD4(+)CD25(+)Foxp3(+) Treg cells was reduced. Importantly, the regulatory function of CD4(+)CD25(+) Treg cells was correspondingly impaired. Together, these results suggest that PZQ can enhance humoral and cellular responses to HBsAg DNA vaccination through inhibition TGF-beta/Smad2,3 signaling.
吡喹酮（PZQ）用于治疗所有形式的血吸虫病，已被证明可诱导强烈的 T 细胞活性并降低 T 调节细胞水平。在我们的研究中，我们研究了 PZQ 是否可作为乙型肝炎表面抗原（HBsAg）DNA 疫苗（pcD-S2）的佐剂，以引发强烈的体液和细胞反应。我们的数据表明，PZQ 作为佐剂可增加 T 细胞增殖和 HBsAg 特异性抗体反应，其特征是 IgG2a/IgG1 的比值更高。此外，还可诱导 CD4(+)和 CD8(+)T 细胞中 IFN-γ水平升高。另外，还观察到明显的抗原特异性细胞毒性 T 淋巴细胞反应。HBsAg 可诱导 TGF-β的表达，而 PZQ 作为佐剂可抑制 TGF-β和 TGF-β/Smad2,3 信号的表达。CD4(+)CD25(+)Foxp3(+)Treg 细胞的频率降低。重要的是，CD4(+)CD25(+)Treg 细胞的调节功能相应受损。总之，这些结果表明，PZQ 可通过抑制 TGF-β/Smad2,3 信号来增强 HBsAg DNA 疫苗接种的体液和细胞反应。
