title: Human antibodies reveal a protective epitope that is highly conserved among human and nonhuman influenza A viruses.
abstract: Influenza remains a serious public health threat throughout the world. Vaccines and antivirals are available that can provide protection from infection. However, new viral strains emerge continuously because of the plasticity of the influenza genome, which necessitates annual reformulation of vaccine antigens, and resistance to antivirals can appear rapidly and become entrenched in circulating virus populations. In addition, the spread of new pandemic strains is difficult to contain because of the time required to engineer and manufacture effective vaccines. Monoclonal antibodies that target highly conserved viral epitopes might offer an alternative protection paradigm. Herein we describe the isolation of a panel of monoclonal antibodies derived from the IgG(+) memory B cells of healthy, human subjects that recognize a previously unknown conformational epitope within the ectodomain of the influenza matrix 2 protein, M2e. This antibody binding region is highly conserved in influenza A viruses, being present in nearly all strains detected to date, including highly pathogenic viruses that infect primarily birds and swine, and the current 2009 swine-origin H1N1 pandemic strain (S-OIV). Furthermore, these human anti-M2e monoclonal antibodies protect mice from lethal challenges with either H5N1 or H1N1 influenza viruses. These results suggest that viral M2e can elicit broadly cross-reactive and protective antibodies in humans. Accordingly, recombinant forms of these human antibodies may provide useful therapeutic agents to protect against infection from a broad spectrum of influenza A strains.
authors.affiliation: Theraclone Sciences, Seattle, WA 98104, USA.
authors.forename: Andres G
authors.initials: AG
authors.lastname: Grandea
authors.forename: Ole A
authors.initials: OA
authors.lastname: Olsen
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Cox
authors.forename: Mark
authors.initials: M
authors.lastname: Renshaw
authors.forename: Philip W
authors.initials: PW
authors.lastname: Hammond
authors.forename: Po-Ying
authors.initials: PY
authors.lastname: Chan-Hui
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Mitcham
authors.forename: Witold
authors.initials: W
authors.lastname: Cieplak
authors.forename: Shaun M
authors.initials: SM
authors.lastname: Stewart
authors.forename: Michael L
authors.initials: ML
authors.lastname: Grantham
authors.forename: Andrew
authors.initials: A
authors.lastname: Pekosz
authors.forename: Maki
authors.initials: M
authors.lastname: Kiso
authors.forename: Kyoko
authors.initials: K
authors.lastname: Shinya
authors.forename: Masato
authors.initials: M
authors.lastname: Hatta
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
authors.forename: Matthew
authors.initials: M
authors.lastname: Moyle
mesh_terms: D000818:Animals; D000906:Antibodies / Q000235:genetics / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology; D001717:Birds; D003429:Cross Reactions / Q000235:genetics / Q000276:immunology; D004196:Disease Outbreaks; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology*; D009980:Influenza A virus / Q000235:genetics* / Q000276:immunology*; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology; D005585:Influenza in Birds / Q000235:genetics / Q000276:immunology*; D007251:Influenza, Human / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008969:Molecular Sequence Data
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D000939:Epitopes; D007252:Influenza Vaccines