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Dev Comp Immunol. 2016 Oct 27. pii: S0145-305X(16)30371-8. doi: 10.1016/j.dci.2016.10.010. [Epub ahead of print]
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.
Wang SF1, Tseng SP2, Loh EW3, Wang WH4, Li MC5, Chen KH6, Tsai WC2, Lee YM7, Chen HY8, Liu FT8, Arthur Chen YM9, Huang JC10.
Author information
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.
Copyright ? 2016. Published by Elsevier Ltd.
KEYWORDS:
Epitope; H1N1; Influenza virus; Monoclonal antibody; Prophylactic; Therapeutic; Trimeric hemagglutinin
PMID: 27984103 DOI: 10.1016/j.dci.2016.10.010
[PubMed - as supplied by publisher]
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.
Wang SF1, Tseng SP2, Loh EW3, Wang WH4, Li MC5, Chen KH6, Tsai WC2, Lee YM7, Chen HY8, Liu FT8, Arthur Chen YM9, Huang JC10.
Author information
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.
Copyright ? 2016. Published by Elsevier Ltd.
KEYWORDS:
Epitope; H1N1; Influenza virus; Monoclonal antibody; Prophylactic; Therapeutic; Trimeric hemagglutinin
PMID: 27984103 DOI: 10.1016/j.dci.2016.10.010
[PubMed - as supplied by publisher]