title: Relationship of the quaternary structure of human secretory IgA to neutralization of influenza virus.
abstract: Secretory IgA (S-IgA) antibodies, the major contributors to humoral mucosal immunity to influenza virus infection, are polymeric Igs present in many external secretions. In the present study, the quaternary structures of human S-IgA induced in nasal mucosa after administration of intranasal inactivated influenza vaccines were characterized in relation to neutralization potency against influenza A viruses. Human nasal IgA antibodies have been shown to contain at least five quaternary structures. Direct and real-time visualization of S-IgA using high-speed atomic force microscopy (AFM) demonstrated that trimeric and tetrameric S-IgA had six and eight antigen-binding sites, respectively, and that these structures exhibited large-scale asynchronous conformational changes while capturing influenza HA antigens in solution. Furthermore, trimeric, tetrameric, and larger polymeric structures, which are minor fractions in human nasal IgA, displayed increased neutralizing potency against influenza A viruses compared with dimeric S-IgA, suggesting that the larger polymeric than dimeric forms of S-IgA play some important roles in protection against influenza A virus infection in the human upper respiratory tract.
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan;
authors.forename: Tadaki
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan;
authors.forename: Akira
authors.initials: A
authors.lastname: Kawaguchi
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan; Influenza Virus Research Center, National Institute of Infectious Diseases, Musashimurayama, Tokyo 208-0011, Japan;
authors.forename: Akira
authors.initials: A
authors.lastname: Ainai
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan;
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Tamura
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan;
authors.forename: Ryo
authors.initials: R
authors.lastname: Ito
authors.affiliation: National Institute of Health Research and Development, Ministry of Health Republic of Indonesia, Jakarta 10560, Indonesia.
authors.forename: Pretty
authors.initials: P
authors.lastname: Multihartina
authors.affiliation: National Institute of Health Research and Development, Ministry of Health Republic of Indonesia, Jakarta 10560, Indonesia.
authors.forename: Vivi
authors.initials: V
authors.lastname: Setiawaty
authors.affiliation: National Institute of Health Research and Development, Ministry of Health Republic of Indonesia, Jakarta 10560, Indonesia.
authors.forename: Krisna Nur Andriana
authors.initials: KN
authors.lastname: Pangesti
authors.affiliation: Influenza Virus Research Center, National Institute of Infectious Diseases, Musashimurayama, Tokyo 208-0011, Japan;
authors.forename: Takato
authors.initials: T
authors.lastname: Odagiri
authors.affiliation: Influenza Virus Research Center, National Institute of Infectious Diseases, Musashimurayama, Tokyo 208-0011, Japan;
authors.forename: Masato
authors.initials: M
authors.lastname: Tashiro
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan; hasegawa@nih.go.jp.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hasegawa
mesh_terms: D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000737:chemistry / Q000276:immunology*; D009500:Neutralization Tests; D009975:Orthomyxoviridae / Q000276:immunology*; D020836:Protein Structure, Quaternary
chemical_list: D007071:Immunoglobulin A, Secretory
keywords: high-speed atomic force microscopy; influenza virus; intranasal inactivated influenza vaccine; secretory IgA