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

// Weidong Zhao 1 , Gan Zhao 1 , Shuren Zhang 1 , Xianzheng Wang 1 , Xueping Yu 2 and Bin Wang 1 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 Correspondence to: Bin Wang, email: bwang3@fudan.edu.cn Keywords: GM-CSF; IFN-α; therapeutic vaccine; HBV; Ly6C hi monocyte Received: April 14, 2017      Accepted: October 30, 2017      Epub: July 13, 2018      Published: September 28, 2018 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 + Ly6C hi 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.