TY - JOUR
T1 - Recombinant human monoclonal antibodies to human cytomegalovirus glycoprotein B neutralize virus in a complement-dependent manner
AU - Ohta, Akane
AU - Fujita, Ayano
AU - Murayama, Tsugiya
AU - Iba, Yoshitaka
AU - Kurosawa, Yoshikazu
AU - Yoshikawa, Tetsushi
AU - Asano, Yoshizo
N1 - Funding Information:
This work was supported by a grant-in-aid from the 21st Century COE Program of Medicine at Fujita Health University, from the Ministry of Education, Culture, Sports, Science and Technology of Japan. This study was also conducted with the support of a grant for Research Promotion of Emerging and Re-emerging Infectious Diseases (H18-Shinko-013) from the Ministry of Health, Labour and Welfare of Japan. We gratefully acknowledge Dr. Yukihiro Nishiyama for helpful suggestions.
PY - 2009/11
Y1 - 2009/11
N2 - 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 VH 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 IgG1 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.
AB - 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 VH 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 IgG1 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.
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U2 - 10.1016/j.micinf.2009.07.010
DO - 10.1016/j.micinf.2009.07.010
M3 - Article
C2 - 19651232
AN - SCOPUS:70349780375
VL - 11
SP - 1029
EP - 1036
JO - Microbes and Infection
JF - Microbes and Infection
SN - 1286-4579
IS - 13
ER -