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

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.

journal_name

EBioMedicine

journal_title

EBioMedicine

authors

Shi B,Wu Y,Wang C,Li X,Yu F,Wang B,Yang Z,Li J,Liang M,Wen Y,Ying T,Yuan Z

doi

10.1016/j.ebiom.2019.10.043

subject

Has Abstract

pub_date

2019-11-01 00:00:00

pages

247-257

issn

2352-3964

pii

S2352-3964(19)30713-3

journal_volume

49

pub_type

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