title: Changes in innate and permissive immune responses after hbv transgenic mouse vaccination and long-term-siRNA treatment [corrected].
abstract: BACKGROUND
  Currently, no licensed therapy can thoroughly eradicate hepatitis B virus (HBV) from the body, including interferon α and inhibitors of HBV reverse-transcription. Small interfering RNA (siRNA) seem to be a promising tool for treating HBV, but had no effect on the pre-existing HBV covalently closed circular DNA. Because it is very difficult to thoroughly eradicate HBV with unique siRNAs, upgrading the immune response is the best method for fighting HBV infection. Here, we aim to explore the immune response of transgenic mice to HBV vaccination after long-term treatment with siRNAs and develop a therapeutic approach that combines siRNAs with immunopotentiators.
  
  
  RESULTS
  To explore the response of transgenic mice to hepatitis B vaccine, innate and acquired immunity were detected after long-term treatment with siRNAs and vaccination. Antiviral cytokines and level of anti-hepatitis B surface antigen antibody (HBsAg-Ab) were measured after three injections of hepatitis B vaccine.
  
  
  RESULTS
  Functional analyses indicated that toll-like receptor-mediated innate immune responses were reinforced, and antiviral cytokines were significantly increased, especially in the pSilencer4.1/HBV groups. Analysis of CD80+/CD86+ dendritic cells in the mouse liver indicated that dendritic cell antigen presentation was strengthened. Furthermore, the siRNA-treated transgenic mice could produce detectable HBsAg-Ab after vaccination, especially in the CpG oligonucleotide vaccine group.
  
  
  CONCLUSIONS
  For the first time, our studies demonstrate that siRNAs with CpG HBV vaccine could strengthen the immune response and break the immune tolerance status of transgenic mice to HBV. Thus, siRNAs and HBV vaccine could provide a sharp double-edged sword against chronic HBV infection.
authors.affiliation: Department of Pediatrics, General Hospital of GuangZhou Military Command of PLA, GuangZhou, China. guangliren@hotmail.com
authors.forename: Guang-Li
authors.initials: GL
authors.lastname: Ren
authors.forename: Guang-Yu
authors.initials: GY
authors.lastname: Huang
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.forename: Ying
authors.initials: Y
authors.lastname: Fang
authors.forename: Heng-Hao
authors.initials: HH
authors.lastname: Ma
authors.forename: Man-Chun
authors.initials: MC
authors.lastname: Xu
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Zhang
authors.forename: Wei-Yun
authors.initials: WY
authors.lastname: Zhang
authors.forename: Ya-Gang
authors.initials: YG
authors.lastname: Zhao
authors.forename: Da-Yong
authors.initials: DY
authors.lastname: Sun
authors.forename: Wen-Kui
authors.initials: WK
authors.lastname: Hu
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D018899:CpG Islands / Q000235:genetics; D016207:Cytokines / Q000276:immunology; D020868:Gene Silencing; D006509:Hepatitis B / Q000517:prevention & control*; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000627:therapeutic use*; D006515:Hepatitis B virus; D007113:Immunity, Innate; D008099:Liver / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009841:Oligonucleotides / Q000235:genetics; D034741:RNA, Small Interfering / Q000627:therapeutic use*; D014611:Vaccination
chemical_list: D016207:Cytokines; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D009841:Oligonucleotides; D034741:RNA, Small Interfering