Recombinant human monoclonal antibodies to human cytomegalovirus glycoprotein B neutralize virus in a complement-dependent manner

Akane Ohta, Ayano Fujita, Tsugiya Murayama, Yoshitaka Iba, Yoshikazu Kurosawa, Tetsushi Yoshikawa, Yoshizo Asano

研究成果: Article査読

10 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1029-1036
ページ数8
ジャーナルMicrobes and Infection
11
13
DOI
出版ステータスPublished - 11-2009

All Science Journal Classification (ASJC) codes

  • 微生物学
  • 免疫学
  • 感染症

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