title: Structural characterization of a protective epitope spanning A(H1N1)pdm09 influenza virus neuraminidase monomers.
abstract: A(H1N1)pdm09 influenza A viruses predominated in the 2013-2014 USA influenza season, and although most of these viruses remain sensitive to Food and Drug Administration-approved neuraminidase (NA) inhibitors, alternative therapies are needed. Here we show that monoclonal antibody CD6, selected for binding to the NA of the prototypic A(H1N1)pdm09 virus, A/California/07/2009, protects mice against lethal virus challenge. The crystal structure of NA in complex with CD6 Fab reveals a unique epitope, where the heavy-chain complementarity determining regions (HCDRs) 1 and 2 bind one NA monomer, the light-chain CDR2 binds the neighbouring monomer, whereas HCDR3 interacts with both monomers. This 30-amino-acid epitope spans the lateral face of an NA dimer and is conserved among circulating A(H1N1)pdm09 viruses. These results suggest that the large, lateral CD6 epitope may be an effective target of antibodies selected for development as therapeutic agents against circulating H1N1 influenza viruses.
authors: Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland 20993, USA.
authors: Hongquan
authors: H
authors: Wan
authors: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, Georgia 30333, USA.
authors: Hua
authors: H
authors: Yang
authors: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, Georgia 30333, USA.
authors: David A
authors: DA
authors: Shore
authors: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, Georgia 30333, USA.
authors: Rebecca J
authors: RJ
authors: Garten
authors: Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland 20993, USA.
authors: Laura
authors: L
authors: Couzens
authors: Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland 20993, USA.
authors: Jin
authors: J
authors: Gao
authors: Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland 20993, USA.
authors: Lianlian
authors: L
authors: Jiang
authors: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, Georgia 30333, USA.
authors: Paul J
authors: PJ
authors: Carney
authors: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, Georgia 30333, USA.
authors: Julie
authors: J
authors: Villanueva
authors: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, Georgia 30333, USA.
authors: James
authors: J
authors: Stevens
authors: Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland 20993, USA.
authors: Maryna C
authors: MC
authors: Eichelberger
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000201:enzymology* / Q000276:immunology*; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000821:virology; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D000596:Amino Acids; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D009439:Neuraminidase