Enhancement of humoral and cellular responses to HBsAg DNA vaccination by immunization with praziquantel through inhibition TGF-beta/Smad2,3 signaling

通过抑制 TGF-β/Smad2,3 信号传导,吡喹酮免疫增强 HBsAg DNA 疫苗的体液和细胞反应

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作者:Qiang Zou, Yiwei Zhong, Hairui Su, Youmin Kang, Jin Jin, Qiang Liu, Shuang Geng, Gan Zhao, Bin Wang

Abstract

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.

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