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Recurring and Adaptable Binding Motifs in Broadly Neutralizing Antibodies to Influenza Virus Are Encoded on the D3-9 Segment of the Ig Gene.

Abstract
Discovery and characterization of broadly neutralizing antibodies (bnAbs) to the influenza hemagglutinin (HA) stem have provided insights for the development of a universal flu vaccine. Identification of signature features common to bnAbs from different individuals will be key to guiding immunogen design. S9-3-37 is a bnAb isolated from a healthy H5N1 vaccinee. Here, structural characterization reveals that the D3-9 gene segment of S9-3-37 contributes most of the interaction surface with the highly conserved stem epitope on HA. Comparison with other influenza bnAb crystal structures indicates that the D3-9 segment provides a general mechanism for targeting HA stem. Interestingly, such bnAbs can approach the HA stem with vastly different angles and orientations. Moreover, D3-9 can be translated in different reading frames in different bnAbs yet still target the same HA stem pocket. Thus, the D3-9 gene segment in the human immune repertoire can provide a robust defense against influenza virus.
AuthorsNicholas C Wu, Seiya Yamayoshi, Mutsumi Ito, Ryuta Uraki, Yoshihiro Kawaoka, Ian A Wilson
JournalCell host & microbe (Cell Host Microbe) Vol. 24 Issue 4 Pg. 569-578.e4 (10 10 2018) ISSN: 1934-6069 [Electronic] United States
PMID30308159 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2018 Elsevier Inc. All rights reserved.
Chemical References
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
Topics
  • Animals
  • Antibodies, Neutralizing (chemistry, genetics, immunology)
  • Antibodies, Viral (chemistry, genetics, immunology)
  • Binding Sites, Antibody (immunology)
  • CHO Cells
  • Cricetulus
  • Epitopes (immunology)
  • Hemagglutinin Glycoproteins, Influenza Virus (chemistry, genetics, immunology)
  • Humans
  • Influenza A Virus, H5N1 Subtype (genetics, immunology)
  • Influenza Vaccines (immunology)
  • Influenza, Human (virology)
  • Reading Frames (immunology)
  • Sequence Analysis, Protein
  • Sf9 Cells

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