In:
eLife, eLife Sciences Publications, Ltd, Vol. 6 ( 2017-09-26)
Abstract:
Hepatitis B virus (HBV) infection is a major global health problem. Currently-available therapies are ineffective in curing chronic HBV infection. HBV and its satellite hepatitis D virus (HDV) infect hepatocytes via binding of the preS1 domain of its large envelope protein to sodium taurocholate cotransporting polypeptide (NTCP). Here, we developed novel human monoclonal antibodies that block the engagement of preS1 with NTCP and neutralize HBV and HDV with high potency. One antibody, 2H5-A14, functions at picomolar level and exhibited neutralization-activity-mediated prophylactic effects. It also acts therapeutically by eliciting antibody-Fc-dependent immunological effector functions that impose durable suppression of viral infection in HBV-infected mice, resulting in reductions in the levels of the small envelope antigen and viral DNA, with no emergence of escape mutants. Our results illustrate a novel antibody-Fc-dependent approach for HBV treatment and suggest 2H5-A14 as a novel clinical candidate for HBV prevention and treatment of chronic HBV infection.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.26738.001
DOI:
10.7554/eLife.26738.002
DOI:
10.7554/eLife.26738.005
DOI:
10.7554/eLife.26738.003
DOI:
10.7554/eLife.26738.004
DOI:
10.7554/eLife.26738.006
DOI:
10.7554/eLife.26738.007
DOI:
10.7554/eLife.26738.008
DOI:
10.7554/eLife.26738.014
DOI:
10.7554/eLife.26738.009
DOI:
10.7554/eLife.26738.010
DOI:
10.7554/eLife.26738.011
DOI:
10.7554/eLife.26738.012
DOI:
10.7554/eLife.26738.013
DOI:
10.7554/eLife.26738.015
DOI:
10.7554/eLife.26738.019
DOI:
10.7554/eLife.26738.016
DOI:
10.7554/eLife.26738.017
DOI:
10.7554/eLife.26738.018
DOI:
10.7554/eLife.26738.020
DOI:
10.7554/eLife.26738.025
DOI:
10.7554/eLife.26738.021
DOI:
10.7554/eLife.26738.022
DOI:
10.7554/eLife.26738.023
DOI:
10.7554/eLife.26738.024
DOI:
10.7554/eLife.26738.026
DOI:
10.7554/eLife.26738.029
DOI:
10.7554/eLife.26738.027
DOI:
10.7554/eLife.26738.028
DOI:
10.7554/eLife.26738.030
DOI:
10.7554/eLife.26738.035
DOI:
10.7554/eLife.26738.036
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2017
detail.hit.zdb_id:
2687154-3
