H7N9 influenza virus neutralizing antibodies that possess few somatic mutations

J Clin Invest. 2016 Apr 1;126(4):1482-94. doi: 10.1172/JCI85317. Epub 2016 Mar 7.


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.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Animals
  • Antibodies, Monoclonal* / genetics
  • Antibodies, Monoclonal* / immunology
  • Antibodies, Neutralizing* / genetics
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Viral* / genetics
  • Antibodies, Viral* / immunology
  • Binding Sites, Antibody / genetics
  • Binding Sites, Antibody / immunology
  • Epitope Mapping
  • Epitopes* / genetics
  • Epitopes* / immunology
  • Female
  • Humans
  • Influenza A Virus, H7N9 Subtype* / genetics
  • Influenza A Virus, H7N9 Subtype* / immunology
  • Influenza Vaccines* / administration & dosage
  • Influenza Vaccines* / genetics
  • Influenza Vaccines* / immunology
  • Male
  • Mice
  • Middle Aged
  • Mutation*


  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes
  • Influenza Vaccines