Publications by authors named "Nina Kallin"

Article Synopsis
  • - Chronic hepatitis B virus (HBV) infection affects 300 million people globally, leading to dysfunction in virus-specific CD8 T cells that struggle to eliminate HBV-infected liver cells due to mechanisms that aren't fully understood.
  • - Research indicates a liver immune rheostat inhibits the activation of these CD8 T cells, particularly the CXCR6 subtype, leading to loss of their functionality, as shown by increased activity of the transcription factor cAMP-responsive element modulator (CREM) in both experimental models and chronic HBV patients.
  • - Enhanced signaling pathways related to cAMP and protein kinase A (PKA) in these T cells contribute to their dysfunction, as they establish prolonged contacts with liver cells, impairing essential activation
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Therapeutic vaccination against chronic hepatitis B must overcome high viral antigen load and local regulatory mechanisms that promote immune-tolerance in the liver and curtail hepatitis B virus (HBV)-specific CD8 T cell immunity. Here, we report that therapeutic heterologous HBcore-protein-prime/Modified-Vaccinia-Virus-Ankara (MVA-HBcore) boost vaccination followed by CpG-application augmented vaccine-induced HBcAg-specific CD8 T cell-function in the liver. In HBV-transgenic as well as AAV-HBV-transduced mice with persistent high-level HBV-replication, the combination of therapeutic vaccination with subsequent CpG-application was synergistic to generate more potent HBV-specific CD8 T cell immunity that improved control of hepatocytes replicating HBV.

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The liver bears unique immune properties that support both immune tolerance and immunity, but the mechanisms responsible for clearance versus persistence of virus-infected hepatocytes remain unclear. Here, we dissect the factors determining the outcome of antiviral immunity using recombinant adenoviruses that reflect the hepatropism and hepatrophism of hepatitis viruses. We generated replication-deficient adenoviruses with equimolar expression of ovalbumin, luciferase, and green fluorescent protein driven by a strong ubiquitous cytomegalovirus (CMV) promoter (Ad-CMV-GOL) or by 100-fold weaker, yet hepatocyte-specific, transthyretin (TTR) promoter (Ad-TTR-GOL).

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