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Title: Human monoclonal antibodies derived from a patient infected with 2009 pandemic influenza A virus broadly cross-neutralize group 1 influenza viruses

Abstract

Highlights: • Influenza infection can elicit heterosubtypic antibodies to group 1 influenza virus. • Three human monoclonal antibodies were generated from an H1N1-infected patient. • The antibodies predominantly recognized α-helical stem of viral hemagglutinin (HA). • The antibodies inhibited HA structural activation during the fusion process. • The antibodies are potential candidates for future antibody therapy to influenza. - Abstract: Influenza viruses are a continuous threat to human public health because of their ability to evolve rapidly through genetic drift and reassortment. Three human monoclonal antibodies (HuMAbs) were generated in this study, 1H11, 2H5 and 5G2, and they cross-neutralize a diverse range of group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H5N1 and H9N2. The three HuMAbs were prepared by fusing peripheral blood lymphocytes from an H1N1pdm-infected patient with a newly developed fusion partner cell line, SPYMEG. All the HuMAbs had little hemagglutination inhibition activity but had strong membrane-fusion inhibition activity against influenza viruses. A protease digestion assay showed the HuMAbs targeted commonly a short α-helix region in the stalk of the hemagglutinin. Furthermore, Ile45Phe and Glu47Gly double substitutions in the α-helix region made the HA unrecognizable by the HuMAbs. These two amino acidmore » residues are highly conserved in the HAs of H1N1, H5N1 and H9N2 viruses. The HuMAbs reported here may be potential candidates for the development of therapeutic antibodies against group 1 influenza viruses.« less

Authors:
 [1];  [1];  [2];  [1];  [3];  [2];  [1];  [2];  [1];  [3];  [2]; ; ;  [1];  [1];  [2];  [1];  [4];  [2];  [1] more »;  [5]; « less
  1. Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan)
  2. (SATREPS), Tokyo (Japan)
  3. (Japan)
  4. (Thailand)
  5. (Egypt)
Publication Date:
OSTI Identifier:
22416615
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 450; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AMINO ACIDS; CELL MEMBRANES; HEMAGGLUTININS; HUMAN POPULATIONS; INFLUENZA; INFLUENZA VIRUSES; INHIBITION; LYMPHOCYTES; MONOCLONAL ANTIBODIES; PATIENTS; RESIDUES; THERAPY

Citation Formats

Pan, Yang, Sasaki, Tadahiro, JST/JICA, Science and Technology Research Partnership for Sustainable Development, Kubota-Koketsu, Ritsuko, Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa, JST/JICA, Science and Technology Research Partnership for Sustainable Development, Inoue, Yuji, JST/JICA, Science and Technology Research Partnership for Sustainable Development, Yasugi, Mayo, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka, JST/JICA, Science and Technology Research Partnership for Sustainable Development, Yamashita, Akifumi, Ramadhany, Ririn, Arai, Yasuha, Du, Anariwa, JST/JICA, Science and Technology Research Partnership for Sustainable Development, Boonsathorn, Naphatsawan, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi, JST/JICA, Science and Technology Research Partnership for Sustainable Development, Ibrahim, Madiha S., Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Damanhour University, Damanhour, and and others. Human monoclonal antibodies derived from a patient infected with 2009 pandemic influenza A virus broadly cross-neutralize group 1 influenza viruses. United States: N. p., 2014. Web. doi:10.1016/J.BBRC.2014.05.060.
Pan, Yang, Sasaki, Tadahiro, JST/JICA, Science and Technology Research Partnership for Sustainable Development, Kubota-Koketsu, Ritsuko, Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa, JST/JICA, Science and Technology Research Partnership for Sustainable Development, Inoue, Yuji, JST/JICA, Science and Technology Research Partnership for Sustainable Development, Yasugi, Mayo, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka, JST/JICA, Science and Technology Research Partnership for Sustainable Development, Yamashita, Akifumi, Ramadhany, Ririn, Arai, Yasuha, Du, Anariwa, JST/JICA, Science and Technology Research Partnership for Sustainable Development, Boonsathorn, Naphatsawan, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi, JST/JICA, Science and Technology Research Partnership for Sustainable Development, Ibrahim, Madiha S., Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Damanhour University, Damanhour, & and others. Human monoclonal antibodies derived from a patient infected with 2009 pandemic influenza A virus broadly cross-neutralize group 1 influenza viruses. United States. doi:10.1016/J.BBRC.2014.05.060.
Pan, Yang, Sasaki, Tadahiro, JST/JICA, Science and Technology Research Partnership for Sustainable Development, Kubota-Koketsu, Ritsuko, Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa, JST/JICA, Science and Technology Research Partnership for Sustainable Development, Inoue, Yuji, JST/JICA, Science and Technology Research Partnership for Sustainable Development, Yasugi, Mayo, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka, JST/JICA, Science and Technology Research Partnership for Sustainable Development, Yamashita, Akifumi, Ramadhany, Ririn, Arai, Yasuha, Du, Anariwa, JST/JICA, Science and Technology Research Partnership for Sustainable Development, Boonsathorn, Naphatsawan, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi, JST/JICA, Science and Technology Research Partnership for Sustainable Development, Ibrahim, Madiha S., Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Damanhour University, Damanhour, and and others. Fri . "Human monoclonal antibodies derived from a patient infected with 2009 pandemic influenza A virus broadly cross-neutralize group 1 influenza viruses". United States. doi:10.1016/J.BBRC.2014.05.060.
@article{osti_22416615,
title = {Human monoclonal antibodies derived from a patient infected with 2009 pandemic influenza A virus broadly cross-neutralize group 1 influenza viruses},
author = {Pan, Yang and Sasaki, Tadahiro and JST/JICA, Science and Technology Research Partnership for Sustainable Development and Kubota-Koketsu, Ritsuko and Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa and JST/JICA, Science and Technology Research Partnership for Sustainable Development and Inoue, Yuji and JST/JICA, Science and Technology Research Partnership for Sustainable Development and Yasugi, Mayo and Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka and JST/JICA, Science and Technology Research Partnership for Sustainable Development and Yamashita, Akifumi and Ramadhany, Ririn and Arai, Yasuha and Du, Anariwa and JST/JICA, Science and Technology Research Partnership for Sustainable Development and Boonsathorn, Naphatsawan and Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi and JST/JICA, Science and Technology Research Partnership for Sustainable Development and Ibrahim, Madiha S. and Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Damanhour University, Damanhour and and others},
abstractNote = {Highlights: • Influenza infection can elicit heterosubtypic antibodies to group 1 influenza virus. • Three human monoclonal antibodies were generated from an H1N1-infected patient. • The antibodies predominantly recognized α-helical stem of viral hemagglutinin (HA). • The antibodies inhibited HA structural activation during the fusion process. • The antibodies are potential candidates for future antibody therapy to influenza. - Abstract: Influenza viruses are a continuous threat to human public health because of their ability to evolve rapidly through genetic drift and reassortment. Three human monoclonal antibodies (HuMAbs) were generated in this study, 1H11, 2H5 and 5G2, and they cross-neutralize a diverse range of group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H5N1 and H9N2. The three HuMAbs were prepared by fusing peripheral blood lymphocytes from an H1N1pdm-infected patient with a newly developed fusion partner cell line, SPYMEG. All the HuMAbs had little hemagglutination inhibition activity but had strong membrane-fusion inhibition activity against influenza viruses. A protease digestion assay showed the HuMAbs targeted commonly a short α-helix region in the stalk of the hemagglutinin. Furthermore, Ile45Phe and Glu47Gly double substitutions in the α-helix region made the HA unrecognizable by the HuMAbs. These two amino acid residues are highly conserved in the HAs of H1N1, H5N1 and H9N2 viruses. The HuMAbs reported here may be potential candidates for the development of therapeutic antibodies against group 1 influenza viruses.},
doi = {10.1016/J.BBRC.2014.05.060},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 450,
place = {United States},
year = {Fri Jul 18 00:00:00 EDT 2014},
month = {Fri Jul 18 00:00:00 EDT 2014}
}