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H7N9 influenza virus neutralizing antibodies that possess few somatic mutations

Academic Article
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Overview

authors

  • Thornburg, N. J.
  • Zhang, H.
  • Bangaru, S.
  • Sapparapu, G.
  • Kose, N.
  • Lampley, R. M.
  • Bombardi, R. G.
  • Yu, Y.
  • Graham, S.
  • Branchizio, A.
  • Yoder, S. M.
  • Rock, M. T.
  • Creech, C. B.
  • Edwards, K. M.
  • Lee, D.
  • Li, S.
  • Wilson, Ian
  • Garcia-Sastre, A.
  • Albrecht, R. A.
  • Crowe Jr., J. E.

publication date

  • 2016

journal

  • Journal of Clinical Investigation  Journal

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.

subject areas

  • Adult
  • Animals
  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Binding Sites, Antibody
  • Epitope Mapping
  • Epitopes
  • Female
  • Humans
  • Influenza A Virus, H7N9 Subtype
  • Influenza Vaccines
  • Male
  • Mice
  • Middle Aged
  • Mutation
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Identity

PubMed Central ID

  • PMC4811156

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/jci85317

PubMed ID

  • 26950424
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Additional Document Info

start page

  • 1482

end page

  • 1494

volume

  • 126

issue

  • 4

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