A mouse model for HBV immunotolerance and immunotherapy.
Lack of an appropriate small animal model remains a major hurdle for studying the immunotolerance and immunopathogenesis induced by hepatitis B virus (HBV) infection. In this study, we report a mouse model with sustained HBV viremia after infection with a recombinant adeno-associated virus (AAV) carrying a replicable HBV genome (AAV/HBV). Similar to the clinical HBV carriers, the mice infected with AAV/HBV were sero-negative for antibodies against HBV surface antigen (HBsAg). Immunization with the conventional HBV vaccine in the presence of aluminum adjuvant failed to elicit an immune response against HBV in these mice. To identify a vaccine that can potentially circumvent this tolerance, the TLR9 agonist CpG was added to HBsAg as an adjuvant. Vaccination of mice with HBsAg/CpG induced not only clearance of viremia, but also strong antibody production and T-cell responses. Furthermore, both the DNA replication and protein expression of HBV were significantly reduced in the livers of AAV/HBV-infected mice. Accordingly, AAV/HBV-infected mice may be used as a robust model for investigating the underlying mechanism(s) of HBV immunotolerance and for developing novel immunotherapies to eradicate HBV infections.
1] IBP-UC Group for Immunotherapy, CAS Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100049, China.
Dan
D
Yang
1] IBP-UC Group for Immunotherapy, CAS Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100049, China.
Longchao
L
Liu
IBP-UC Group for Immunotherapy, CAS Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Danming
D
Zhu
IBP-UC Group for Immunotherapy, CAS Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Hua
H
Peng
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Lishan
L
Su
1] IBP-UC Group for Immunotherapy, CAS Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China [2] Department of Pathology, the University of Chicago, 924E, 57 Street, Chicago, IL 60637.
Yang-Xin
YX
Fu
IBP-UC Group for Immunotherapy, CAS Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Liguo
L
Zhang
D000818:Animals; D015153:Blotting, Western; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006509:Hepatitis B / Q000276:immunology / Q000628:therapy* / Q000821:virology; D006510:Hepatitis B Antibodies / Q000097:blood / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000627:therapeutic use*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D007114:Immunization; D007124:Immunoenzyme Techniques; D007167:Immunotherapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014766:Viremia / Q000276:immunology / Q000821:virology
D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; D012333:RNA, Messenger