title: The adjuvant effects of co-stimulatory molecules on cellular and memory responses to HBsAg DNA vaccination.
abstract: Because DNA vaccines on their own tend to induce weak immune responses in humans, adjuvant methods are needed in order to improve their efficacy. The co-stimulatory molecules 4-1BBL, OX40L, and CD70 have been shown to induce strong T cell activities; therefore, in this study, we investigated whether they may be used as molecular adjuvants for a hepatitis B surface antigen (HBsAg) DNA vaccine (pcDS2) in eliciting strong cellular and memory responses. Compared to mice immunized with pcDS2 alone, addition of the co-stimulatory molecules increased T cell proliferation and an HBsAg-specific antibody response that was marked with a higher ratio of IgG2a/IgG1. Importantly, pcDS2 plus these co-stimulatory molecules elicited a higher level of IFN-gamma and IL-4 in CD4(+) T cells and a higher level of IFN-gamma in CD8(+) T cells. In addition, a significantly robust antigen-specific cytotoxic T lymphocyte (CTL) response and the production of long-term memory CD8(+) T cells were also observed in the groups immunized with pcDS2 plus 4-1BBL, OX40L, or CD70. Consistently, as late as 100 days after immunization, upregulated expressions of BCL-2, Spi2A, IL-7Ra, and IL-15Ra were still observed in mice immunized with pcDS2 plus these co-stimulatory molecules, suggesting the generation of memory T cells in these groups. Together, these results suggest that the co-stimulatory molecules 4-1BBL, OX40L, or CD70 can enhance the immunogenicity of HBsAg DNA vaccines, resulting in strong humoral, cellular, and memory responses. This approach may lead to an effective therapeutic vaccine for chronic hepatitis B virus (HBV) infection.
authors.affiliation: State Key Laboratory for Agro-Biotechnology, Department of Microbiology and Immunology, College of Biological Science, China Agricultural University, Beijing 100094, China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Du
authors.forename: Guoxing
authors.initials: G
authors.lastname: Zheng
authors.forename: Huali
authors.initials: H
authors.lastname: Jin
authors.forename: Youmin
authors.initials: Y
authors.lastname: Kang
authors.forename: Junpeng
authors.initials: J
authors.lastname: Wang
authors.forename: Chong
authors.initials: C
authors.lastname: Xiao
authors.forename: Shuo
authors.initials: S
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.forename: Aoshuang
authors.initials: A
authors.lastname: Chen
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
mesh_terms: D053330:4-1BB Ligand / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000276:Adjuvants, Immunologic / Q000235:genetics*; D000818:Animals; D053282:CD27 Ligand / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006367:HeLa Cells; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D053278:OX40 Ligand / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D048069:Tumor Necrosis Factors / Q000235:genetics*; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D053330:4-1BB Ligand; D000276:Adjuvants, Immunologic; D053282:CD27 Ligand; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D007074:Immunoglobulin G; D053278:OX40 Ligand; D011994:Recombinant Proteins; D048069:Tumor Necrosis Factors; D019444:Vaccines, DNA