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

Sheng Fan Wang, Sung Pin Tseng, El Wui Loh, Wen Hung Wang, Ming Chun Li, Kuan Hsuan Chen, Wan Chi Tsai, Yuan Ming Lee, Huan Yuan Chen, Fu Tong Liu, Yi Ming Arthur Chen, Jason C. Huang

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)8-17
Number of pages10
JournalDevelopmental and Comparative Immunology
Volume67
DOIs
Publication statusPublished - Feb 1 2017

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Developmental Biology

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