title: A broadly protective therapeutic antibody against influenza B virus with two mechanisms of action.
abstract: Influenza B virus (IBV) causes annual influenza epidemics around the world. Here we use an in vivo plasmablast enrichment technique to isolate a human monoclonal antibody, 46B8 that neutralizes all IBVs tested in vitro and protects mice against lethal challenge of all IBVs tested when administered 72 h post infection. 46B8 demonstrates a superior therapeutic benefit over Tamiflu and has an additive antiviral effect in combination with Tamiflu. 46B8 binds to a conserved epitope in the vestigial esterase domain of hemagglutinin (HA) and blocks HA-mediated membrane fusion. After passage of the B/Brisbane/60/2008 virus in the presence of 46B8, we isolated three resistant clones, all harbouring the same mutation (Ser301Phe) in HA that abolishes 46B8 binding to HA at low pH. Interestingly, 46B8 is still able to protect mice against lethal challenge of the mutant viruses, possibly owing to its ability to mediate antibody-dependent cellular cytotoxicity (ADCC).
authors.affiliation: Department of Infectious Diseases, Genentech, South San Francisco, California 94080, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Chai
authors.affiliation: Department of Infectious Diseases, Genentech, South San Francisco, California 94080, USA.
authors.forename: Lee R
authors.initials: LR
authors.lastname: Swem
authors.affiliation: Department of Translational Immunology, Genentech, South San Francisco, California 94080, USA.
authors.forename: Summer
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Antibody Engineering, Genentech, South San Francisco, California 94080, USA.
authors.forename: Gerald
authors.initials: G
authors.lastname: Nakamura
authors.affiliation: Department of Antibody Engineering, Genentech, South San Francisco, California 94080, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Chiang
authors.affiliation: Department of Structural Biology, Genentech, South San Francisco, California 94080, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Estevez
authors.affiliation: Department of Structural Biology, Genentech, South San Francisco, California 94080, USA.
authors.forename: Rina
authors.initials: R
authors.lastname: Fong
authors.affiliation: Department of BioAnalytical Sciences, Genentech, South San Francisco, California 94080, USA.
authors.forename: Lynn
authors.initials: L
authors.lastname: Kamen
authors.affiliation: Department of BioAnalytical Sciences, Genentech, South San Francisco, California 94080, USA.
authors.forename: Elviza
authors.initials: E
authors.lastname: Kho
authors.affiliation: Department of Pathology, Genentech, South San Francisco, California 94080, USA.
authors.forename: Mike
authors.initials: M
authors.lastname: Reichelt
authors.affiliation: Department of Translational Immunology, Genentech, South San Francisco, California 94080, USA.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Biochemical and Cellular Pharmacology, Genentech, South San Francisco, California 94080, USA.
authors.forename: Henry
authors.initials: H
authors.lastname: Chiu
authors.affiliation: Department of Bioinformatics and Computational Biology, Genentech, South San Francisco, California 94080, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Skippington
authors.affiliation: Department of Molecular Biology, Genentech, South San Francisco, California 94080, USA.
authors.forename: Zora
authors.initials: Z
authors.lastname: Modrusan
authors.affiliation: Department of Molecular Biology, Genentech, South San Francisco, California 94080, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Stinson
authors.affiliation: Department of Translational Immunology, Genentech, South San Francisco, California 94080, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Structural Biology, Genentech, South San Francisco, California 94080, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lupardus
authors.affiliation: Department of Structural Biology, Genentech, South San Francisco, California 94080, USA.
authors.forename: Claudio
authors.initials: C
authors.lastname: Ciferri
authors.affiliation: Department of Infectious Diseases, Genentech, South San Francisco, California 94080, USA.
authors.forename: Man-Wah
authors.identifier: 0000-0002-7748-212X
authors.initials: MW
authors.lastname: Tan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000627:therapeutic use*; D000939:Epitopes; D006388:Hemagglutinins; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007074:Immunoglobulin G / Q000276:immunology / Q000627:therapeutic use*; D009981:Influenza B virus; D051379:Mice; D008958:Models, Molecular; D009976:Orthomyxoviridae Infections / Q000628:therapy* / Q000821:virology; D053139:Oseltamivir; D011487:Protein Conformation
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000939:Epitopes; D006388:Hemagglutinins; D007074:Immunoglobulin G; D053139:Oseltamivir