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

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.

Authors:
; ; ; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
OTHERNIH
OSTI Identifier:
1128584
Resource Type:
Journal Article
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 5; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Lee, Peter S., Ohshima, Nobuko, Stanfield, Robyn L., Yu, Wenli, Iba, Yoshitaka, Okuno, Yoshinobu, Kurosawa, Yoshikazu, and Wilson, Ian A. Receptor mimicry by antibody F045–092 facilitates universal binding to the H3 subtype of influenza virus. United States: N. p., 2014. Web. doi:10.1038/ncomms4614.
Lee, Peter S., Ohshima, 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. United States. https://doi.org/10.1038/ncomms4614
Lee, Peter S., Ohshima, Nobuko, Stanfield, Robyn L., Yu, Wenli, Iba, Yoshitaka, Okuno, Yoshinobu, Kurosawa, Yoshikazu, and Wilson, Ian A. 2014. "Receptor mimicry by antibody F045–092 facilitates universal binding to the H3 subtype of influenza virus". United States. https://doi.org/10.1038/ncomms4614.
@article{osti_1128584,
title = {Receptor mimicry by antibody F045–092 facilitates universal binding to the H3 subtype of influenza virus},
author = {Lee, Peter S. and Ohshima, Nobuko and Stanfield, Robyn L. and Yu, Wenli and Iba, Yoshitaka and Okuno, Yoshinobu and Kurosawa, Yoshikazu and Wilson, Ian A.},
abstractNote = {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.},
doi = {10.1038/ncomms4614},
url = {https://www.osti.gov/biblio/1128584}, journal = {Nature Communications},
issn = {2041-1723},
number = ,
volume = 5,
place = {United States},
year = {Thu Apr 10 00:00:00 EDT 2014},
month = {Thu Apr 10 00:00:00 EDT 2014}
}