title: Cimetidine synergizes with Praziquantel to enhance the immune response of HBV DNA vaccine via activating cytotoxic CD8(+) T cell.
abstract: Previously, we have reported that either CIM or PZQ, 2 clinical drugs, could be used to develop as adjuvants on HBV DNA vaccine to elicit both humoral and cellular immune responses. Here, we demonstrate that combinations of CIM and PZQ as adjuvants for a HBV DNA vaccine, could induce much stronger antigen specific CD4(+) and CD8(+) T cell responses compared either with CIM or PZQ alone. The synergistic effects of CIM plus PZQ to HBV DNA vaccine were observed on a higher IgG2a/IgG1 ratio, an increase of HBsAg-specific CD4(+) T cells capable of producing IFN-γ or IL-17A and a robust IFN-γ-, IL-17A-, or TNF-α-producing CD8(+) T cells to HBsAg. Most importantly, the antigen-specific CTL response was also elevated significantly, which is critical for the eradication of hepatitis B virus (HBV) infected cells. Using an HBsAg transgenic mouse model, the expression of HBsAg in the hepatic cells was also significantly reduced after immunized with pCD-S 2 in the presence of 0.5% CIM and 0.25% PZQ. Further investigations demonstrated that the synergistic effects of combination of CIM and PZQ were dependent on enhanced cytotoxic CD8(+) T cells, which was correlated with impaired activities of regulatory T cells. Therefore, combinations of CIM and PZQ have great potential to be used as effective adjuvants on DNA-based vaccinations for the treatment of chronic hepatitis B.
authors.affiliation: State Key Laboratory for Agro-Biotechnology; College of Biological Science; China Agricultural University; Beijing, PR China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xie
authors.affiliation: Key Laboratory of Medical Molecular Virology of MOH and MOE; Fudan University Shanghai Medical College; Shanghai, PR China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Geng
authors.affiliation: State Key Laboratory for Agro-Biotechnology; College of Biological Science; China Agricultural University; Beijing, PR China.
authors.forename: Hu
authors.initials: H
authors.lastname: Liu
authors.affiliation: Key Laboratory of Medical Molecular Virology of MOH and MOE; Fudan University Shanghai Medical College; Shanghai, PR China.
authors.forename: Chaofan
authors.initials: C
authors.lastname: Li
authors.affiliation: Shanghai Public Health Clinical Center affiliated to Fudan University; Shanghai, PR China.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory for Agro-Biotechnology; College of Biological Science; China Agricultural University; Beijing, PR China; Key Laboratory of Medical Molecular Virology of MOH and MOE; Fudan University Shanghai Medical College; Shanghai, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002927:Cimetidine / Q000008:administration & dosage*; D016207:Cytokines / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011223:Praziquantel / Q000008:administration & dosage*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D011223:Praziquantel; D002927:Cimetidine
keywords: Cimetidine; HBV DNA vaccine; Praziquantel; adjuvant; cytotoxic CD8+ T cell