Human
antibodies specific for
HCMV are currently considered as potential anti-HCMV therapeutic agents. In this study, we used a combinatorial human
antibody library to isolate and characterize complete human
monoclonal antibodies that effectively neutralize
HCMV in a complement-dependent manner. One hundred and six clones were isolated in two independent screens using
HCMV virions and recombinant
glycoprotein B, gB654, as
antigens. All of the clones recognized the same molecule gB and were classified into 14 groups based on the
amino acid sequence of the V(H) region. Seven representative clones from these 14 groups had a strong gB654 binding affinity by
surface plasmon resonance (SPR). A pairwise binding competition analysis suggested that there were three groups based on differences in the gB
recognition sites. Although
Fab fragments of the seven groups showed strong affinity for gB, none of the
Fab fragments neutralized
HCMV infectivity in vitro. In contrast, complete human
IgG(1)
antibodies of at least three groups neutralized
HCMV in a complement-dependent manner. These data suggest that potent therapeutic
antibodies can be obtained from a human
antibody library, including most of the functional
antibodies that mediate
humoral immunity to the
selected pathogen.
