A site of vulnerability on the influenza virus hemagglutinin head domain trimer interface

Bangaru, Sandhya, Lang, Shanshan, Schotsaert, Michael, Vanderven, Hillary A., Zhu, Xueyong, Kose, Nurgun, Bombardi, Robin, Finn, Jessica A., Kent, Stephen J., Gilchuk, Pavlo, Gilchuk, Iuliia, Turner, Hannah L., García-Sastre, Adolfo, Li, Sheng, Ward, Andrew B., Wilson, Ian A., and Crowe, James E. (2019) A site of vulnerability on the influenza virus hemagglutinin head domain trimer interface. Cell, 177 (5). e.18. pp. 1136-1152.

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Abstract

Here, we describe the discovery of a naturally occurring human antibody (Ab), FluA-20, that recognizes a new site of vulnerability on the hemagglutinin (HA) head domain and reacts with most influenza A viruses. Structural characterization of FluA-20 with H1 and H3 head domains revealed a novel epitope in the HA trimer interface, suggesting previously unrecognized dynamic features of the trimeric HA protein. The critical HA residues recognized by FluA-20 remain conserved across most subtypes of influenza A viruses, which explains the Ab's extraordinary breadth. The Ab rapidly disrupted the integrity of HA protein trimers, inhibited cell-to-cell spread of virus in culture, and protected mice against challenge with viruses of H1N1, H3N2, H5N1, or H7N9 subtypes when used as prophylaxis or therapy. The FluA-20 Ab has uncovered an exceedingly conserved protective determinant in the influenza HA head domain trimer interface that is an unexpected new target for anti-influenza therapeutics and vaccines.

Item ID: 59789
Item Type: Article (Research - C1)
ISSN: 1097-4172
Funders: National Institutes of Health (NIH), National Center for Advancing Translational Sciences (NCATS), National Institute of Allergy and Infectious Disease (NIAID)
Projects and Grants: NIH U19 AI117905, NIH R56 AI12737, NIH P01 AI097092, NIH HSN272201400024C, NIH HHSN272201400008C, NCAT CTSA award No. UL1 TR00224, NIAID HHSN27220170041
Date Deposited: 03 Sep 2019 02:47
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110705 Humoural Immunology and Immunochemistry @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 50%
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