title: Oral administered particulate yeast-derived glucan promotes hepatitis B virus clearance in a hydrodynamic injection mouse model.
abstract: Hepatitis B virus (HBV) persistent infection is associated with ineffective immune response for the clearance of virus. Immunomodulators represent an important class of therapeutics, which potentially could be beneficial for the treatment of HBV infection. The particulate yeast-derived glucan (PYDG) has been shown to enhance the innate and adaptive immune responses. We therefore, assessed the efficacy of PYDG in enhancing HBV specific immune responses by employing the hydrodynamic injection-based (HDI) HBV transfection mouse model. Mice were intragatric administered PYDG daily for 9 weeks post pAAV/HBV1.2 hydrodynamic injection. PYDG treatment significantly promoted HBV DNA clearance and production of HBsAb compared to control mice. PYDG treatment resulted in recruitment of macrophages, dendritic cells (DCs) and effector T cells to the liver microenvironment, accompanied by a significantly augmented DCs maturation and HBV-specific IFN-γ and TNF-α production by T cell. In addition, enhanced production of Th1 cytokines in liver tissue interstitial fluid (TIF) was associated with PYDG administration. Live imaging showed the accumulation of PYDG in the mouse liver. Our results demonstrate that PYDG treatment significantly enhances HBV-specific Th1 immune responses, accompanied by clearance of HBV DNA, and therefore holds promise for further development of therapeutics against chronic hepatitis B.
authors: Shanghai Public Health Clinical Center, Fudan University, Shanghai, China; Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
authors: Xiaoyu
authors: X
authors: Yu
authors: Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors: Dandan
authors: D
authors: Zhang
authors: Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
authors: Bisheng
authors: B
authors: Shi
authors: Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
authors: Guangxu
authors: G
authors: Ren
authors: Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors: Xiuhua
authors: X
authors: Peng
authors: Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
authors: Zhong
authors: Z
authors: Fang
authors: Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, K1H 8M5, Canada.
authors: Maya
authors: M
authors: Kozlowski
authors: Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors: Xiaohui
authors: X
authors: Zhou
authors: Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors: Xiaonan
authors: X
authors: Zhang
authors: Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors: Min
authors: M
authors: Wu
authors: Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors: Cong
authors: C
authors: Wang
authors: Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
authors: Zhenghong
authors: Z
authors: Yuan
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects / Q000276:immunology*; D000818:Animals; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D005936:Glucans / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D006515:Hepatitis B virus / Q000187:drug effects* / Q000276:immunology / Q000472:pathogenicity; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000737:chemistry; D007267:Injections; D008099:Liver / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D012441:Saccharomyces cerevisiae / Q000737:chemistry; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology
chemical_list: D005936:Glucans; D007155:Immunologic Factors