@article{07df5368c77b447bbea2ca14cf237a25,
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.",
keywords = "Epitope, H1N1, Influenza virus, Monoclonal antibody, Prophylactic, Therapeutic, Trimeric hemagglutinin",
author = "Wang, {Sheng Fan} and Tseng, {Sung Pin} and Loh, {El Wui} and Wang, {Wen Hung} and Li, {Ming Chun} and Chen, {Kuan Hsuan} and Tsai, {Wan Chi} and Lee, {Yuan Ming} and Chen, {Huan Yuan} and Liu, {Fu Tong} and {Arthur Chen}, {Yi Ming} and Huang, {Jason C.}",
note = "Funding Information: The authors wish to thank the staff from Taipei Veterans General Hospital and Taiwan CDC for their assistance in influenza virus identification and support, and Professor Suh-Chin Wu at the Institute of Biotechnology and Department of Life Science, National Tsing Hua University, Hsinchu, for the preparation of tri-rHA. We also thank Dr. Jia-Tsrong Jan at the Genomic Research Center, Academia Sinica for the assistance in mice challenge assay and Miss Esmeralda Erazo for language editing. This work was supported by grants from the Ministry of Science and Technology, Taiwan, R.O.C. ( MOST-105-2321-B-037-001 and MOST-104-2321-B-037-001 to SFW and YMAC, respectively) and ( MOST 101-2320-B-010-055 – MY3 to JCH) and from the Ministry of Education, Aiming for the Top University Plan to JCH at National Yang-Ming University. This study also supported by grants from the Center for Infectious Disease and Cancer Research, Kaohsiung Medical University ( KMUTP104E04 ), and partially by the Kaohsiung Medical University Research Foundation ( KMU-Q105010 ). Publisher Copyright: {\textcopyright} 2016 Elsevier Ltd",
year = "2017",
month = feb,
day = "1",
doi = "10.1016/j.dci.2016.10.010",
language = "English",
volume = "67",
pages = "8--17",
journal = "Developmental and Comparative Immunology",
issn = "0145-305X",
publisher = "Elsevier Limited",
}