title: A human monoclonal antibody derived from a vaccinated volunteer recognizes heterosubtypically a novel epitope on the hemagglutinin globular head of H1 and H9 influenza A viruses.
abstract: Most neutralizing antibodies elicited during influenza virus infection or by vaccination have a narrow spectrum because they usually target variable epitopes in the globular head region of hemagglutinin (HA). In this study, we describe a human monoclonal antibody (HuMAb), 5D7, that was prepared from the peripheral blood lymphocytes of a vaccinated volunteer using the fusion method. The HuMAb heterosubtypically neutralizes group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H9N2, with a strong hemagglutinin inhibition activity. Selection of an escape mutant showed that the HuMAb targets a novel conformational epitope that is located in the HA head region but is distinct from the receptor binding site. Furthermore, Phe114Ile substitution in the epitope made the HA unrecognizable by the HuMAb. Amino acid residues in the predicted epitope region are also highly conserved in the HAs of H1N1 and H9N2. The HuMAb reported here may be a potential candidate for the development of therapeutic/prophylactic antibodies against H1 and H9 influenza viruses.
authors.affiliation: Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi, Thailand; Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo, Japan.
authors.forename: Naphatsawan
authors.initials: N
authors.lastname: Boonsathorn
authors.affiliation: Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi, Thailand; Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo, Japan.
authors.forename: Sumolrat
authors.initials: S
authors.lastname: Panthong
authors.affiliation: Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi, Thailand.
authors.forename: Sarawut
authors.initials: S
authors.lastname: Koksunan
authors.affiliation: National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi, Thailand.
authors.forename: Malinee
authors.initials: M
authors.lastname: Chittaganpitch
authors.affiliation: National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi, Thailand.
authors.forename: Siripaporn
authors.initials: S
authors.lastname: Phuygun
authors.affiliation: National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi, Thailand.
authors.forename: Sunthareeya
authors.initials: S
authors.lastname: Waicharoen
authors.affiliation: Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi, Thailand; Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo, Japan.
authors.forename: Apichai
authors.initials: A
authors.lastname: Prachasupap
authors.affiliation: Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo, Japan.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa, Japan.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Kubota-Koketsu
authors.affiliation: Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka, Japan.
authors.forename: Mayo
authors.initials: M
authors.lastname: Yasugi
authors.affiliation: Ina Laboratory, Medical & Biological Laboratories Corporation, Ltd., Ina, Nagano, Japan; Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo, Japan.
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Ono
authors.affiliation: Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
authors.forename: Yasuha
authors.initials: Y
authors.lastname: Arai
authors.affiliation: Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kurosu
authors.affiliation: Food and Drug Administration, Ministry of Public Health, Muang, Nonthaburi, Thailand.
authors.forename: Pathom
authors.initials: P
authors.lastname: Sawanpanyalert
authors.affiliation: Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo, Japan. Electronic address: Ikuta@biken.osaka-u.ac.jp.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Ikuta
authors.affiliation: Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo, Japan. Electronic address: nabe@biken.osaka-u.ac.jp.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Watanabe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D057134:Antibodies, Neutralizing / Q000096:biosynthesis*; D000914:Antibodies, Viral / Q000096:biosynthesis*; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology; D056738:Cross Protection; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000276:immunology; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053127:Influenza A Virus, H9N2 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D014611:Vaccination; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; C483468:hemagglutinin, human influenza A virus
keywords: Conserved epitope in HA head region; Heterosubtypic neutralizing antibody; Human monoclonal antibody; Influenza A virus