Preclinical evaluation of two human anti-hepatitis B virus (HBV) monoclonal antibodies in the HBV-Trimera mouse model and in HBV chronic carrier chimpanzees
R. Eren et al., Preclinical evaluation of two human anti-hepatitis B virus (HBV) monoclonal antibodies in the HBV-Trimera mouse model and in HBV chronic carrier chimpanzees, HEPATOLOGY, 32(3), 2000, pp. 588-596
Two human monoclonal antibodies (mAbs) against hepatitis B surface antigen
(HBsAg) generated in the Trimera mouse system are described. Both mAbs 17.1
.41 and 19.79.5 are of the IgG1 isotype and have high affinity constants fo
r HBsAg binding in the range of 10(-10) mol/L. Monoclonal antibody 17.1.41
recognizes a conformational epitope on the a determinant of HBsAg whereas m
Ab 19.79.5 recognizes a linear one. The 2 mAbs bind to a panel of hepatitis
B virus (HBV) subtypes with distinct patterns, The neutralizing activity o
f these antibodies was tested in 2 different animal model systems. Administ
ration of each mAb to HBV-Trimera mice, a system that provides a mouse mode
l for human hepatitis B infection, reduced the viral load and the percentag
e of HBV-DNA-positive mice in a dose-dependent manner. These 2 mAbs were mo
re effective than a polyclonal antibody preparation (Hepatect; Biotest Phar
ma, Dreieich, Germany) in both inhibition of HBV liver infection and reduct
ion of viral load. A single administration of a mixture of these mAbs into
HBV chronic carrier chimpanzees resulted in immediate reduction in HBsAg le
vels followed by recurrence to initial levels within few days. Thus, these
mAbs may be potential candidates for preventive therapy or in combination w
ith other antiviral agents against HBV. Further studies in humans are neede
d to assess these mAbs in various clinical indications.