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
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Weidong Zhao1, Gan Zhao1, Shuren Zhang1, Xianzheng Wang1, Xueping Yu2 and Bin Wang1
1Key Laboratory of Medical Molecular Virology of The Ministry of Health and Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai, China
2Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
Bin Wang, email: [email protected]
Keywords: GM-CSF; IFN-α; therapeutic vaccine; HBV; Ly6Chi monocyte
Received: April 14, 2017 Accepted: October 30, 2017 Epub: July 13, 2018 Published: September 28, 2018
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.
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