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Oncotarget. 2018 Jul 13;9(76):34213-34228. doi: 10.18632/oncotarget.25789. eCollection 2018 Sep 28.
Clearance of HBeAg and HBsAg of HBV in mice model by a recombinant HBV vaccine combined with GM-CSF and IFN-α as an effective therapeutic vaccine adjuvant.
Zhao W1, Zhao G1, Zhang S1, Wang X1, Yu X2, Wang B1.
Author information
1
Key Laboratory of Medical Molecular Virology of The Ministry of Health and Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai, China.
2
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
Abstract
Chronic hepatitis B virus (CHB) infection is a significant public threat. Current interferon-α (IFN-α) based therapies and anti-viral drugs have failed to clear the infection in the majority of CHB patients and animal models. In our previous study, we established a combined protocol that employed a 3-day pretreatment with granulocyte-macrophage colony stimulating factor (GM-CSF) prior to a standard HBV vaccine. It achieved a 90% reduction of HBsAg level in the HBsAg transgenic mouse model. This protocol, while effective, remains too complex for clinical use. In this study, we formulated a new regimen by combining GM-CSF, IFN-α and a recombinant HBV vaccine (GM-CSF/IFN-α/VACCINE) into a single preparation and tested its efficacy in a HBV infection model. After four vaccinations, both serum HBeAg and HBsAg were cleared, accompanied by a 95% reduction of HBV+ hepatocytes and the presence of a large number of infiltrating CD8+ T cells in the liver. Mechanistically these robust responses were initiated by a vaccine-induced conversion of CCR2-dependent CD11b+Ly6Chi monocytes into CD11b+CD11c+ DCs. This finding sheds light on the potential mechanism of action of the GM-CSF-based vaccine adjuvant and provides definable markers for clinical assessment during future testing of such highly potent vaccine protocols in HBV patients.
KEYWORDS:
GM-CSF; HBV; IFN-α; Ly6Chi monocyte; therapeutic vaccine
PMID:
30344938
PMCID:
PMC6188151
DOI:
10.18632/oncotarget.25789 |
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