title: Generation and characterization of new monoclonal antibodies against swine origin 2009 influenza A (H1N1) virus and evaluation of their prophylactic and therapeutic efficacy in a mouse model.
abstract: In 2009, a swine-origin influenza A virus - A(H1N1)pdm09 - emerged and has became a pandemic strain circulating worldwide. The hemagglutinin (HA) of influenza virus is a potential target for the development of anti-viral therapeutic agents. Here, we generated mAbs by immunization of baculovirus-insect expressing trimeric recombinant HA of the A(H1N1)pdm09 strain. Results indicated that the mAbs recognized two novel neutralizing and protective epitopes-"STAS" and "FRSK" which located near Cb and Ca1 antigenic regions respectively and were conserved in almost 2009-2016 influenza H1N1 stains. The mAb 12E11 demonstrated higher protective efficacy than mAb 8B10 in mice challenge assay. Both mAb pretreatments significantly reduced virus titers and pro-inflammatory cytokines in mice lung postinfection (p < 0.01), and showed prophylactic and therapeutic efficacies even 48 h postinfection (p < 0.05). Combination therapy using the mAbs with oseltamivir pre- and post-treatment showed synergistic therapeutic effect in mice model (p < 0.01). Further investigation for clinical application in humans is warranted.
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. Electronic address: wasf1234@kmu.edu.tw.
authors.forename: Sheng-Fan
authors.initials: SF
authors.lastname: Wang
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
authors.forename: Sung-Pin
authors.initials: SP
authors.lastname: Tseng
authors.affiliation: Center for Evidence-based Health Care, Taipei Medical University, Shuang Ho Hospital, New Taipei City 23561, Taiwan.
authors.forename: El-Wui
authors.initials: EW
authors.lastname: Loh
authors.affiliation: Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
authors.forename: Wen-Hung
authors.initials: WH
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Taipei City Hospital, Yang-Ming Branch, Taipei 11146, Taiwan.
authors.forename: Ming-Chun
authors.initials: MC
authors.lastname: Li
authors.affiliation: Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
authors.forename: Kuan-Hsuan
authors.initials: KH
authors.lastname: Chen
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
authors.forename: Wan-Chi
authors.initials: WC
authors.lastname: Tsai
authors.affiliation: Department of Laboratory Medicine, National Yang-Ming University Hospital, Yi-Lan 260, Taiwan.
authors.forename: Yuan-Ming
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11578, Taiwan; Department of Dermatology, University of California at Davis, CA 95816, USA.
authors.forename: Huan-Yuan
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11578, Taiwan; Department of Dermatology, University of California at Davis, CA 95816, USA.
authors.forename: Fu-Tong
authors.initials: FT
authors.lastname: Liu
authors.affiliation: Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Department of Microbiology, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. Electronic address: arthur@kmu.edu.tw.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Arthur Chen
authors.affiliation: Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei 11272, Taiwan; AIDS Prevention and Research Center, National Yang-Ming University, Taipei 11272, Taiwan. Electronic address: jchuang2@ym.edu.tw.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Huang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000302:isolation & purification / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004285:Dogs; D004357:Drug Synergism; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000628:therapy*; D053139:Oseltamivir / Q000627:therapeutic use; D055503:Protein Multimerization; D013552:Swine; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D016056:Immunodominant Epitopes; D014765:Viral Vaccines; D053139:Oseltamivir
keywords: Epitope; H1N1; Influenza virus; Monoclonal antibody; Prophylactic; Therapeutic; Trimeric hemagglutinin