Combination therapy including CpG oligodeoxynucleotides and entecavir induces early viral response and enhanced inhibition of viral replication in a woodchuck model of chronic hepadnaviral infection
| Autor: | Ejuan Zhang, Thekla Kemper, Mengji Lu, Jörg Vollmer, Wolfram H. Gerlich, Michael Roggendorf, Xiaoyong Zhang, Rongjuan Pei, Dieter Glebe, Heather L. Davis, Zhongji Meng |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Guanine CpG Oligodeoxynucleotide viruses medicine.medical_treatment Medizin Virus Replication Antiviral Agents Random Allocation 03 medical and health sciences Hepatitis B Chronic Interferon Virology medicine Animals Hepatitis B Virus Woodchuck Hepatitis B Antibodies Pharmacology biology Woodchuck hepatitis virus Interferon-alpha TLR9 Entecavir Immunotherapy biochemical phenomena metabolism and nutrition biology.organism_classification digestive system diseases Disease Models Animal 030104 developmental biology Oligodeoxyribonucleotides Viral replication CpG site Marmota DNA Viral Immunology Leukocytes Mononuclear Drug Therapy Combination medicine.drug |
| Zdroj: | Antiviral Research. 125:14-24 |
| ISSN: | 0166-3542 |
| Popis: | CpG oligodeoxynucleotides (ODNs) stimulate immune cells via TLR9 and are potentially useful immunomodulators for the treatment of chronic viral infections. In the present study, different classes of CpGs were tested for their capacities for innate immune activation and antiviral activities in the woodchuck model. A class P CpG ODN was found to stimulate interferon (IFN) production in woodchuck peripheral blood mononuclear cells (PBMCs) in vitro, and following subcutaneous administration in vivo, it was observed to induce IFN and MxA expression in woodchuck PBMCs. Combination treatment with CpG ODN and entecavir (ETV) led to effective suppression of the woodchuck hepatitis virus (WHV) load in the woodchucks, with early viral responses and inhibition of replication. The woodchuck hepatitis surface antigen (WHsAg) serum concentrations were strongly decreased by CpG and ETV together but not by either agent alone, indicating synergistic effects. However, viral control post-treatment was still transient, similar to that observed with ETV alone. Significantly elevated levels of serum aspartate aminotransferase (AST) but not of alanine aminotransferase (ALT) in some of the woodchucks receiving CpG ODN were noted, but these increases were resolved before the completion of treatment and were not associated with an elevated serum bilirubin level or coagulation disorders, suggesting the absence of a significant safety concern. |
| Databáze: | OpenAIRE |
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