title: Human monoclonal antibodies derived from a patient infected with 2009 pandemic influenza A virus broadly cross-neutralize group 1 influenza viruses.
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.
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
authors.forename: Yang
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo, Japan.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa, Japan; JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo, Japan.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Kubota-Koketsu
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka, Japan; JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo, Japan.
authors.forename: Mayo
authors.initials: M
authors.lastname: Yasugi
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Yamashita
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
authors.forename: Ririn
authors.initials: R
authors.lastname: Ramadhany
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
authors.forename: Yasuha
authors.initials: Y
authors.lastname: Arai
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo, Japan.
authors.forename: Anariwa
authors.initials: A
authors.lastname: Du
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi, Thailand; JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo, Japan.
authors.forename: Naphatsawan
authors.initials: N
authors.lastname: Boonsathorn
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Egypt.
authors.forename: Madiha S
authors.initials: MS
authors.lastname: Ibrahim
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; Department of Infectious Diseases, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan.
authors.forename: Tomo
authors.initials: T
authors.lastname: Daidoji
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; Department of Infectious Diseases, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan; JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Nakaya
authors.affiliation: Ina Laboratory, Medical & Biological Laboratories Corporation, Ltd., Ina, Nagano, Japan; JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo, Japan.
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Ono
authors.affiliation: Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Okuno
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo, Japan. Electronic address: Ikuta@biken.osaka-u.ac.jp.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Ikuta
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo, Japan. Electronic address: nabe@biken.osaka-u.ac.jp.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology; D002460:Cell Line; D000882:Haplorhini; D006388:Hemagglutinins / Q000276:immunology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology*; D007668:Kidney / Q000276:immunology / Q000821:virology; D009500:Neutralization Tests
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D006388:Hemagglutinins
keywords: Cross-neutralizing antibody; Global epitope; Human monoclonal antibody; Influenza A virus