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Dev Comp Immunol. 2017 Feb;67:8-17. doi: 10.1016/j.dci.2016.10.010. Epub 2016 Oct 27.

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.

Author information

1
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.
2
Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
3
Center for Evidence-based Health Care, Taipei Medical University, Shuang Ho Hospital, New Taipei City 23561, Taiwan.
4
Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
5
Department of Pediatrics, Taipei City Hospital, Yang-Ming Branch, Taipei 11146, Taiwan.
6
Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
7
Department of Laboratory Medicine, National Yang-Ming University Hospital, Yi-Lan 260, Taiwan.
8
Institute of Biomedical Sciences, Academia Sinica, Taipei 11578, Taiwan; Department of Dermatology, University of California at Davis, CA 95816, USA.
9
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.
10
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.

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.

KEYWORDS:

Epitope; H1N1; Influenza virus; Monoclonal antibody; Prophylactic; Therapeutic; Trimeric hemagglutinin

PMID:
27984103
DOI:
10.1016/j.dci.2016.10.010
[Indexed for MEDLINE]

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