Receptor mimicry by antibody F045-092 facilitates universal binding to the H3 subtype of influenza virus

Peter S. Lee, Nobuko Oshima, Robyn L. Stanfield, Wenli Yu, Yoshitaka Iba, Yoshinobu Okuno, Yoshikazu Kurosawa, Ian A. Wilson

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Influenza viruses present a significant health challenge each year, as in the H3N2 epidemic of 2012-2013. Here we describe an antibody, F045-092, that possesses broadly neutralizing activity against the entire H3 subtype and accommodates the natural variation and additional glycosylation in all strains tested from 1963 to 2011. Crystal structures of F045-092 in complex with HAs from 1975 and 2011 H3N2 viruses reveal the structural basis for its neutralization breadth through insertion of its 23-residue HCDR3 into the receptor-binding site that involves striking receptor mimicry. F045-092 extends its recognition to divergent subtypes, including H1, H2 and H13, using the enhanced avidity of its IgG to overcome lower-affinity Fab binding, as observed with other antibodies that target the receptor-binding site. This unprecedented level of antibody cross-reactivity against the H3 subtype can potentially inform on development of a pan-H3 vaccine or small-molecule therapeutics.

Original languageEnglish
Article number3614
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 10-04-2014

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influenza
viruses
Orthomyxoviridae
antibodies
Viruses
Antibodies
Binding Sites
H3N2 Subtype Influenza A Virus
vaccines
Glycosylation
health
affinity
insertion
Vaccines
reactivity
Immunoglobulin G
Crystal structure
Health
crystal structure
Molecules

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Lee, Peter S. ; Oshima, Nobuko ; Stanfield, Robyn L. ; Yu, Wenli ; Iba, Yoshitaka ; Okuno, Yoshinobu ; Kurosawa, Yoshikazu ; Wilson, Ian A. / Receptor mimicry by antibody F045-092 facilitates universal binding to the H3 subtype of influenza virus. In: Nature Communications. 2014 ; Vol. 5.
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Receptor mimicry by antibody F045-092 facilitates universal binding to the H3 subtype of influenza virus. / Lee, Peter S.; Oshima, Nobuko; Stanfield, Robyn L.; Yu, Wenli; Iba, Yoshitaka; Okuno, Yoshinobu; Kurosawa, Yoshikazu; Wilson, Ian A.

In: Nature Communications, Vol. 5, 3614, 10.04.2014.

Research output: Contribution to journalArticle

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