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Knockdown of Virus Antigen Expression Increases Therapeutic Vaccine Efficacy in High-titer HBV Carrier Mice.
Michler, Thomas Kosinska, Anna D Festag, Julia Bunse, Till Su, Jinpeng Ringelhan, Marc Imhof, Hortenzia Grimm, Dirk Steiger, Katja Mogler, Carolin
Michler, Thomas
Kosinska, Anna D
Festag, Julia
Bunse, Till
Su, Jinpeng
Ringelhan, Marc
Imhof, Hortenzia
Grimm, Dirk
Steiger, Katja
Mogler, Carolin
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2020-01-28
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Abstract
In both models of HBV infection, mice that express hepatocyte-specific small hairpin RNAs or that were given subcutaneous injections of siRNAs had reduced levels of HBV antigens, HBV replication, and viremia (1-3 log10 reduction), compared to mice given control RNAs. Vaccination induced production of HBV-neutralizing antibodies, and increased numbers and functionality of HBV-specific, CD8+ T-cells in mice with low, but not in mice with high levels of HBV antigen. Mice with initially high titers of HBV and knockdown of HBV antigen expression, but not mice with reduced viremia following administration of entecavir, developed polyfunctional, HBV-specific CD8+ T cells and HBV was eliminated.
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Gastroenterology. 2020 Jan 28. pii: S0016-5085(20)30125-6. doi: 10.1053/j.gastro.2020.01.032.
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en
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1528-0012
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Attribution-NonCommercial-ShareAlike 4.0 International