复旦hbv三明治免疫疗法（英文版）

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https://www.sciencedirect.com/sc ... i/S2352396419307133

齐欢畅

Evaluation of antiviral - passive - active immunization (“sandwich”) therapeutic strategy for functional cure of chronic hepatitis B in mice

Author links open overlay panelBishengShiabYanlingWuaChunyuWangaXiaofangLiaFanYuaBinWangaZhenlinYangacJianhuaLiaMifangLiangdYumeiWenaTianleiYingaZhenghongYuana
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https://doi.org/10.1016/j.ebiom.2019.10.043Get rights and content
Under a Creative Commons licenseopen access
Abstract
Background
Chronic Hepatitis B (CHB) remains a major problem for global public health. Viral persistence and immune defects are the two major reasons for CHB, and it was hypothesized that based on a transient clearance of serum viral DNA and HBsAg “window stage”, active immunization against hepatitis B virus (HBV) might initiate effective host immune responses versus HBV to achieve functional cure of CHB.

Methods
Two experimental mouse models that mice hydrodynamic injected HBV DNA or infected with recombinant AAV/HBV were used. The “sandwich” therapeutic effect by using a potent human anti-HBsAg neutralizing monoclonal antibody (G12) in combination with antiviral drug tenofovir disoproxil fumarate (TDF), followed by active immunization with HBsAg-HBsAb (mYIC) was evaluated.

Findings
A single G12 injection rapidly cleared serum HBsAg in HDI-HBV carrier mice, with a synergistic effect in decreasing viral DNA load when TDF was given orally. When both serum viral DNA and HBsAg load became low or undetectable, mYIC was administered. A more effective clearance of viral DNA and HBsAg was observed and serum HBsAb was developed only in these “sandwich”-treated mice. Efficient intrahepatic anti-HBV immune responses were also observed in these mice, including the formation of aggregates of myeloid cells with CD8+ T cells and increased TNF-α, granzyme B production.

Interpretation
The “sandwich” combination therapy not only efficiently decreased HBsAg and HBV DNA levels but also induced effective cellular and humoral immunity, which may result in functional cure of CHB.

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Keywords
Chronic hepatitis BHBsAbTDFHBsAg-HBsAb immune complexLiver CD8+ T cells
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© 2019 The Authors. Published by Elsevier B.V.