title: On a mouse monoclonal antibody that neutralizes all four dengue virus serotypes.
abstract: The flavivirus envelope glycoprotein (E) is responsible for viral attachment and entry by membrane fusion. Its ectodomain is the primary target of the humoral immune response. In particular, the C-terminal Ig-like domain III of E, which is exposed at the surface of the viral particle, forms an attractive antigen for raising protective monoclonal antibodies (mAb). 9F12, a mouse mAb raised against a dengue virus (DENV) serotype 2 recombinant domain III, cross-reacts with corresponding domains from the other three DENV serotypes and also with West Nile virus. mAb 9F12 binds with nanomolar affinity to a conserved epitope that maps to the viral surface comprising residues 305, 307, 310 and 330 of the E protein. mAb 9F12 neutralizes all four DENV serotypes in plaque reduction assays. We expressed a single-chain Fv from 9F12 that retains the binding activity of the parent mAb. Adsorption and fusion inhibition assays indicate that mAb 9F12 prevents early steps of viral entry. Its virus inhibition activity and broad cross-reactivity makes mAb 9F12 a suitable candidate for optimization and humanization into a therapeutic antibody to treat severe infections by dengue.
authors.affiliation: Program in Emerging Infectious Diseases, Duke-NUS, Graduate Medical School, Singapore.|School of Biological Sciences, Nanyang Technological University, Biopolis, Singapore.
authors.forename: Ravikumar
authors.initials: R
authors.lastname: Rajamanonmani
authors.affiliation: Novartis Institute for Tropical Diseases, Biopolis, Singapore.
authors.forename: Celine
authors.initials: C
authors.lastname: Nkenfou
authors.affiliation: Department of Biochemistry and Molecular Biology, James Cook University, Australia.
authors.forename: Paula
authors.initials: P
authors.lastname: Clancy
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Biopolis, Singapore.
authors.forename: Yin Hoe
authors.initials: YH
authors.lastname: Yau
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Biopolis, Singapore.
authors.forename: Susana Geifman
authors.initials: SG
authors.lastname: Shochat
authors.affiliation: Departments of Medicine, Molecular Microbiology, Pathology and Immunology, Washington University School of Medicine, St Louis, USA.
authors.forename: Soila
authors.initials: S
authors.lastname: Sukupolvi-Petty
authors.affiliation: Novartis Institute for Tropical Diseases, Biopolis, Singapore.
authors.forename: Wouter
authors.initials: W
authors.lastname: Schul
authors.affiliation: Departments of Medicine, Molecular Microbiology, Pathology and Immunology, Washington University School of Medicine, St Louis, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
authors.affiliation: Program in Emerging Infectious Diseases, Duke-NUS, Graduate Medical School, Singapore.|Department of Biochemistry and Molecular Biology, James Cook University, Australia.
authors.forename: Subhash G
authors.initials: SG
authors.lastname: Vasudevan
authors.affiliation: AFMB CNRS UMR6098, Marseille, France.|School of Biological Sciences, Nanyang Technological University, Biopolis, Singapore.
authors.forename: Julien
authors.initials: J
authors.lastname: Lescar
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003429:Cross Reactions; D003715:Dengue / Q000276:immunology; D003716:Dengue Virus / Q000145:classification* / Q000235:genetics / Q000276:immunology*; D018604:Epitope Mapping; D008561:Membrane Fusion / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D012703:Serotyping; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D014759:Viral Envelope Proteins