title: H7N9 influenza virus neutralizing antibodies that possess few somatic mutations.
abstract: Avian H7N9 influenza viruses are group 2 influenza A viruses that have been identified as the etiologic agent for a current major outbreak that began in China in 2013 and may pose a pandemic threat. Here, we examined the human H7-reactive antibody response in 75 recipients of a monovalent inactivated A/Shanghai/02/2013 H7N9 vaccine. After 2 doses of vaccine, the majority of donors had memory B cells that secreted IgGs specific for H7 HA, with dominant responses against single HA subtypes, although frequencies of H7-reactive B cells ranged widely between donors. We isolated 12 naturally occurring mAbs with low half-maximal effective concentrations for binding, 5 of which possessed neutralizing and HA-inhibiting activities. The 5 neutralizing mAbs exhibited narrow breadth of reactivity with influenza H7 strains. Epitope-mapping studies using neutralization escape mutant analysis, deuterium exchange mass spectrometry, and x-ray crystallography revealed that these neutralizing mAbs bind near the receptor-binding pocket on HA. All 5 neutralizing mAbs possessed low numbers of somatic mutations, suggesting the clones arose from naive B cells. The most potent mAb, H7.167, was tested as a prophylactic treatment in a mouse intranasal virus challenge study, and systemic administration of the mAb markedly reduced viral lung titers.
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Thornburg
authors.forename: Heng
authors.initials: H
authors.lastname: Zhang
authors.forename: Sandhya
authors.initials: S
authors.lastname: Bangaru
authors.forename: Gopal
authors.initials: G
authors.lastname: Sapparapu
authors.forename: Nurgun
authors.initials: N
authors.lastname: Kose
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Lampley
authors.forename: Robin G
authors.initials: RG
authors.lastname: Bombardi
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Yu
authors.forename: Stephen
authors.initials: S
authors.lastname: Graham
authors.forename: Andre
authors.initials: A
authors.lastname: Branchizio
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Yoder
authors.forename: Michael T
authors.initials: MT
authors.lastname: Rock
authors.forename: C Buddy
authors.initials: CB
authors.lastname: Creech
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Edwards
authors.forename: David
authors.initials: D
authors.lastname: Lee
authors.forename: Sheng
authors.initials: S
authors.lastname: Li
authors.forename: Ian A
authors.initials: IA
authors.lastname: Wilson
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.forename: Randy A
authors.initials: RA
authors.lastname: Albrecht
authors.forename: James E
authors.initials: JE
authors.lastname: Crowe
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000235:genetics / Q000276:immunology; D000914:Antibodies, Viral / Q000235:genetics / Q000276:immunology; D001666:Binding Sites, Antibody / Q000235:genetics / Q000276:immunology; D018604:Epitope Mapping; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000235:genetics / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009154:Mutation
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D007252:Influenza Vaccines