title: Human antibodies that neutralize respiratory droplet transmissible H5N1 influenza viruses.
abstract: Recent studies described the experimental adaptation of influenza H5 HAs that confers respiratory droplet transmission (rdt) to influenza virus in ferrets. Acquisition of the ability to transmit via aerosol may lead to the development of a highly pathogenic pandemic H5 virus. Vaccines are predicted to play an important role in H5N1 control should the virus become readily transmissible between humans. We obtained PBMCs from patients who received an A/Vietnam/1203/2004 H5N1 subunit vaccine. Human hybridomas were then generated and characterized. We identified antibodies that bound the HA head domain and recognized both WT and rdt H5 HAs. We used a combination of structural techniques to define a mechanism of antibody recognition of an H5 HA receptor-binding site that neutralized H5N1 influenza viruses and pseudoviruses carrying the HA rdt variants that have mutations near the receptor-binding site. Incorporation or retention of this critical antigenic site should be considered in the design of novel H5 HA immunogens to protect against mammalian-adapted H5N1 mutants.
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Thornburg
authors.forename: David P
authors.initials: DP
authors.lastname: Nannemann
authors.forename: David L
authors.initials: DL
authors.lastname: Blum
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Belser
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Tumpey
authors.forename: Shyam
authors.initials: S
authors.lastname: Deshpande
authors.forename: Gloria A
authors.initials: GA
authors.lastname: Fritz
authors.forename: Gopal
authors.initials: G
authors.lastname: Sapparapu
authors.forename: Jens C
authors.initials: JC
authors.lastname: Krause
authors.forename: Jeong Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Ward
authors.forename: David E
authors.initials: DE
authors.lastname: Lee
authors.forename: Sheng
authors.initials: S
authors.lastname: Li
authors.forename: Katie L
authors.initials: KL
authors.lastname: Winarski
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Spiller
authors.forename: Jens
authors.initials: J
authors.lastname: Meiler
authors.forename: James E
authors.initials: JE
authors.lastname: Crowe
mesh_terms: D000595:Amino Acid Sequence; D057134:Antibodies, Neutralizing / Q000737:chemistry* / Q000378:metabolism; D000914:Antibodies, Viral / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D018604:Epitope Mapping; D006801:Humans; D006825:Hybridomas; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control* / Q000635:transmission / Q000821:virology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D014611:Vaccination
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral