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

Vaccine. 2010 Feb 23;28(8):2032-8. doi: 10.1016/j.vaccine.2009.10.101.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • CHO Cells
  • Cell Proliferation
  • Cricetinae
  • Cricetulus
  • Female
  • Gene Expression Regulation
  • Hepatitis B Antibodies / blood
  • Hepatitis B Antibodies / immunology
  • Hepatitis B Surface Antigens / immunology*
  • Hepatitis B Vaccines / immunology*
  • Immunity, Cellular
  • Immunity, Humoral
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Lymphocyte Culture Test, Mixed
  • Mice
  • Mice, Inbred C57BL
  • Praziquantel / pharmacology*
  • Signal Transduction
  • Smad2 Protein / immunology
  • Smad2 Protein / metabolism
  • Smad3 Protein / immunology
  • Smad3 Protein / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / metabolism
  • Vaccines, DNA / immunology*

Substances

  • Adjuvants, Immunologic
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines
  • Immunoglobulin G
  • Smad2 Protein
  • Smad2 protein, mouse
  • Smad3 Protein
  • Smad3 protein, mouse
  • Transforming Growth Factor beta
  • Vaccines, DNA
  • Praziquantel