title: Nanoparticles encapsulating hepatitis B virus cytosine-phosphate-guanosine induce therapeutic immunity against HBV infection.
abstract: Infection with hepatitis B virus (HBV) is the most common cause of liver disease worldwide. However, because the current interferon (IFN)-based treatments have toxic side effects and marginal efficacy, improved antivirals are essential. Here we report that unmethylated cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODNs) from the HBV genome (HBV-CpG) induced robust expression of IFN-α by plasmacytoid dendritic cells (pDCs) in a Toll-like receptor 9 (TLR9)-dependent manner. We also identified inhibitory guanosine-rich ODNs in the HBV genome (HBV-ODN) that are capable of inhibiting HBV-CpG-induced IFN-α production. Furthermore, nanoparticles containing HBV-CpG, termed NP(HBV-CpG), reversed the HBV-ODN-mediated suppression of IFN-α production and also exerted a strong immunostimulatory effect on lymphocytes. Our results suggest that NP(HBV-CpG) can enhance the immune response to hepatitis B surface antigen (HBsAg) and skew this response toward the Th1 pathway in mice immunized with rHBsAg and NP(HBV-CpG). Moreover, NP(HBV-CpG)-based therapy led to the efficient clearance of HBV and induced an anti-HBsAg response in HBV carrier mice.
  
  
  CONCLUSIONS
  Endogenous HBV-CpG ODNs from the HBV genome induce IFN-α production so that nanoparticle-encapsulated HBV-CpG may act as an HBsAg vaccine adjuvant and may also represent a potent therapeutic agent for the treatment of chronic HBV infection.
authors.affiliation: Institute of Immunology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, China; Department of Microbiology, Anhui Medical University, Hefei, China.
authors.forename: Shujuan
authors.initials: S
authors.lastname: Lv
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Shuang
authors.initials: S
authors.lastname: Dou
authors.forename: Xianzhu
authors.initials: X
authors.lastname: Yang
authors.forename: Xiang
authors.initials: X
authors.lastname: Ni
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
authors.forename: Haiming
authors.initials: H
authors.lastname: Wei
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003596:Cytosine; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006151:Guanosine; D006509:Hepatitis B / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D006514:Hepatitis B Surface Antigens / Q000494:pharmacology / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000627:therapeutic use*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology / Q000627:therapeutic use*; D010710:Phosphates; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D006514:Hepatitis B Surface Antigens; D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides; D010710:Phosphates; D011994:Recombinant Proteins; D006151:Guanosine; D003596:Cytosine