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

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1029-1036
Number of pages8
JournalMicrobes and Infection
Volume11
Issue number13
DOIs
Publication statusPublished - 01-11-2009

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Cercopithecine Herpesvirus 1
Monoclonal Antibodies
Antibodies
Immunoglobulin Fab Fragments
Clone Cells
Surface Plasmon Resonance
Humoral Immunity
Virion
Simplexvirus glycoprotein B
Amino Acid Sequence
Glycoproteins
Immunoglobulin G
Antigens
Therapeutics

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Ohta, Akane ; Fujita, Ayano ; Murayama, Tsugiya ; Iba, Yoshitaka ; Kurosawa, Yoshikazu ; Yoshikawa, Tetsushi ; Asano, Yoshizo. / Recombinant human monoclonal antibodies to human cytomegalovirus glycoprotein B neutralize virus in a complement-dependent manner. In: Microbes and Infection. 2009 ; Vol. 11, No. 13. pp. 1029-1036.
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Recombinant human monoclonal antibodies to human cytomegalovirus glycoprotein B neutralize virus in a complement-dependent manner. / Ohta, Akane; Fujita, Ayano; Murayama, Tsugiya; Iba, Yoshitaka; Kurosawa, Yoshikazu; Yoshikawa, Tetsushi; Asano, Yoshizo.

In: Microbes and Infection, Vol. 11, No. 13, 01.11.2009, p. 1029-1036.

Research output: Contribution to journalArticle

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