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.
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Authors | Nicholas C Wu, Seiya Yamayoshi, Mutsumi Ito, Ryuta Uraki, Yoshihiro Kawaoka, Ian A Wilson |
Journal | Cell host & microbe
(Cell Host Microbe)
Vol. 24
Issue 4
Pg. 569-578.e4
(10 10 2018)
ISSN: 1934-6069 [Electronic] United States |
PMID | 30308159
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2018 Elsevier Inc. All rights reserved. |
Chemical References |
- Antibodies, Neutralizing
- Antibodies, Viral
- Epitopes
- Hemagglutinin Glycoproteins, Influenza Virus
- Influenza Vaccines
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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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