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 sust...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/H BV 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/H BV-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.展开更多
Viral pneumonia is a major cause of mortality caused by both systemic and respiratory infections.The danger-associated molecular patterns(DAMPs)released during cell death in viral infection may cause a self-propagatin...Viral pneumonia is a major cause of mortality caused by both systemic and respiratory infections.The danger-associated molecular patterns(DAMPs)released during cell death in viral infection may cause a self-propagating inflammatory response with lasting lung damage.The CD24–Siglec 10/G interaction is an emerging immune checkpoint that regulates inflammation caused by DAMPs.1,2,3 While we have demonstrated that fortifying this immune checkpoint can reduce inflammation in the colon,4 joints5 and central nervous system,6 it is unclear whether CD24Fc can protect against pneumonia.To address this issue,we evaluated the lung pathology of simian immunodeficiency virus(SIV)-infected rhesus monkeys that received either normal saline(NS)or CD24Fc.展开更多
文摘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/H BV 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/H BV-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.
基金This work was supported in part by grants from the Key Scientific and Technological Program of China(2013ZX10001002-001,2014ZX10005-002,2017ZX10202102-001-005)OncoImmune,Inc.and the National Natural Science Foundation of China(81601808,81671627,U1802284).
文摘Viral pneumonia is a major cause of mortality caused by both systemic and respiratory infections.The danger-associated molecular patterns(DAMPs)released during cell death in viral infection may cause a self-propagating inflammatory response with lasting lung damage.The CD24–Siglec 10/G interaction is an emerging immune checkpoint that regulates inflammation caused by DAMPs.1,2,3 While we have demonstrated that fortifying this immune checkpoint can reduce inflammation in the colon,4 joints5 and central nervous system,6 it is unclear whether CD24Fc can protect against pneumonia.To address this issue,we evaluated the lung pathology of simian immunodeficiency virus(SIV)-infected rhesus monkeys that received either normal saline(NS)or CD24Fc.
