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
| Autor: | Jason C. Huang, Wen Hung Wang, Ming Chun Li, Wan-Chi Tsai, Sheng-Fan Wang, Fu-Tong Liu, Kuan Hsuan Chen, Yi Ming Arthur Chen, El Wui Loh, Yuan Ming Lee, Huan Yuan Chen, Sung-Pin Tseng |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Swine medicine.drug_class viruses Immunology Hemagglutinin (influenza) Hemagglutinin Glycoproteins Influenza Virus Antibodies Viral Monoclonal antibody medicine.disease_cause Virus Epitope Madin Darby Canine Kidney Cells Mice 03 medical and health sciences Dogs Influenza A Virus H1N1 Subtype Oseltamivir 0302 clinical medicine Orthomyxoviridae Infections Antigen Influenza Human medicine Influenza A virus Animals Humans 030212 general & internal medicine Mice Inbred BALB C biology Immunodominant Epitopes Antibodies Monoclonal virus diseases Drug Synergism Viral Vaccines Combined Modality Therapy Virology Titer 030104 developmental biology Immunization biology.protein Immunotherapy Protein Multimerization Developmental Biology |
| Zdroj: | Developmental & Comparative Immunology. 67:8-17 |
| ISSN: | 0145-305X 2009-2016 |
| DOI: | 10.1016/j.dci.2016.10.010 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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