title: Cross-protection of newly emerging HPAI H5 viruses by neutralizing human monoclonal antibodies: A viable alternative to oseltamivir.
abstract: Newly emerging highly pathogenic avian influenza (HPAI) H5N2, H5N3, H5N5, H5N6, H5N8 and H5N9 viruses have been spreading in poultry and wild birds. The H5N6 viruses have also caused 10 human infections with 4 fatal cases in China. Here, we assessed the cross-neutralization and cross-protection of human and mouse monoclonal antibodies against 2 viruses: a HPAI H5N8 virus, A/chicken/Netherlands/14015526/2014 (NE14) and a HPAI H5N6 virus, A/Sichuan/26221/2014 (SC14). The former was isolated from an infected chicken in Netherlands in 2014 and the latter was isolated from an infected human patient in Sichuan, China. We show that antibodies FLA5.10, FLD21.140, 100F4 and 65C6, but not AVFluIgG01, AVFluIgG03, S139/1 and the VRC01 control, potently cross-neutralize the H5N8 NE14 and H5N6 SC14 viruses. Furthermore, we show that a single injection of >1 mg/kg of antibody 100F4 at 4 hours before, or 20 mg/kg antibody 100F4 at 72 hours after, a lethal dose of H5N8 NE14 enables mice to withstand the infection. Finally, we show that a single injection of 0.5 or 1 mg/kg antibody 100F4 prophylactically or 10 mg/kg 100F4 therapeutically outperforms a 5-day course of 10 mg/kg/day oseltamivir treatment against lethal H5N8 NE14 or H5N6 SC14 infection in mice. Our results suggest that further preclinical evaluation of human monoclonal antibodies against newly emerging H5 viruses is warranted.
authors.affiliation: a Unit of Antiviral Immunity and Genetic Therapy, Institut Pasteur of Shanghai , Chinese Academy of Sciences , Shanghai , China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Ren
authors.affiliation: a Unit of Antiviral Immunity and Genetic Therapy, Institut Pasteur of Shanghai , Chinese Academy of Sciences , Shanghai , China.
authors.forename: Guiqin
authors.initials: G
authors.lastname: Wang
authors.affiliation: a Unit of Antiviral Immunity and Genetic Therapy, Institut Pasteur of Shanghai , Chinese Academy of Sciences , Shanghai , China.
authors.forename: Shuangshuang
authors.initials: S
authors.lastname: Wang
authors.affiliation: b The University of Hong Kong, Hong Kong Special Administrative Region , China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Chen
authors.affiliation: b The University of Hong Kong, Hong Kong Special Administrative Region , China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Chen
authors.affiliation: a Unit of Antiviral Immunity and Genetic Therapy, Institut Pasteur of Shanghai , Chinese Academy of Sciences , Shanghai , China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Hu
authors.affiliation: c University of California , Los Angeles , CA , USA.
authors.forename: Genhong
authors.initials: G
authors.lastname: Cheng
authors.affiliation: a Unit of Antiviral Immunity and Genetic Therapy, Institut Pasteur of Shanghai , Chinese Academy of Sciences , Shanghai , China.
authors.forename: Paul
authors.initials: P
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D002645:Chickens; D002681:China; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D000071225:Influenza A Virus, H5N8 Subtype / Q000276:immunology*; D005585:Influenza in Birds / Q000235:genetics / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D053139:Oseltamivir / Q000627:therapeutic use; D014764:Viral Proteins / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D057134:Antibodies, Neutralizing; D000998:Antiviral Agents; D014764:Viral Proteins; D053139:Oseltamivir; C487630:NA protein, influenza A virus; D009439:Neuraminidase
keywords: Cross-protection; hemagglutinin; highly pathogenic avian influenza virus; human monoclonal antibody; newly emerging H5 viruses; oseltamivir