Structures of Hepatitis B Virus Core- and e-Antigen Immune Complexes Suggest Multi-point Inhibition.
Structure
; 26(10): 1314-1326.e4, 2018 10 02.
Article
in En
| MEDLINE
| ID: mdl-30100358
ABSTRACT
Hepatitis B virus (HBV) is the leading cause of liver disease worldwide. While an adequate vaccine is available, current treatment options are limited, not highly effective, and associated with adverse effects, encouraging the development of alternative therapeutics. The HBV core gene encodes two different proteins core, which forms the viral nucleocapsid, and pre-core, which serves as an immune modulator with multiple points of action. The two proteins mostly have the same sequence, although they differ at their N and C termini and in their dimeric arrangements. Previously, we engineered two human-framework antibody fragments (Fab/scFv) with nano- to picomolar affinities for both proteins. Here, by means of X-ray crystallography, analytical ultracentrifugation, and electron microscopy, we demonstrate that the antibodies have non-overlapping epitopes and effectively block biologically important assemblies of both proteins. These properties, together with the anticipated high tolerability and long half-lives of the antibodies, make them promising therapeutics.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hepatitis B virus
/
Hepatitis B Core Antigens
/
Hepatitis B e Antigens
/
Antibodies, Monoclonal
Limits:
Animals
/
Humans
Language:
En
Journal:
Structure
Journal subject:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
BIOTECNOLOGIA
Year:
2018
Document type:
Article
Affiliation country:
United States