A Site of Vulnerability on the Influenza Virus Hemagglutinin Head Domain Trimer Interface

Sandhya Bangaru; Shanshan Lang; Michael Schotsaert; Hillary A. Vanderven; Xueyong Zhu; Nurgun Kose; Robin Bombardi; Jessica A. Finn; Stephen J. Kent; Pavlo Gilchuk; Iuliia Gilchuk; Hannah L. Turner; Adolfo García-Sastre; Sheng Li; Andrew B. Ward; Ian A. Wilson; James E. Crowe

doi:10.1016/j.cell.2019.04.011

A Site of Vulnerability on the Influenza Virus Hemagglutinin Head Domain Trimer Interface

Sandhya Bangaru, Shanshan Lang, Michael Schotsaert, Hillary A. Vanderven, Xueyong Zhu, Nurgun Kose, Robin Bombardi, Jessica A. Finn, Stephen J. Kent, Pavlo Gilchuk, Iuliia Gilchuk, Hannah L. Turner, Adolfo García-Sastre, Sheng Li, Andrew B. Ward, Ian A. Wilson, James E. Crowe

Research output: Contribution to journal › Article › peer-review

128 Scopus citations

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. Antibodies targeting a novel site in the head domain of hemagglutinin afford broad protection against influenza.

Original language	English
Pages (from-to)	1136-1152.e18
Journal	Cell
Volume	177
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2019.04.011
State	Published - 16 May 2019

Keywords

B-lymphocytes
antibodies
antibodies
antibody-dependent cell cytotoxicity
antigen-antibody reactions
hemagglutinin glycoproteins
influenza A virus
influenza virus
monoclonal
viral

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Bangaru, S., Lang, S., Schotsaert, M., Vanderven, H. A., Zhu, X., Kose, N., Bombardi, R., Finn, J. A., Kent, S. J., Gilchuk, P., Gilchuk, I., Turner, H. L., García-Sastre, A., Li, S., Ward, A. B., Wilson, I. A., & Crowe, J. E. (2019). A Site of Vulnerability on the Influenza Virus Hemagglutinin Head Domain Trimer Interface. Cell, 177(5), 1136-1152.e18. https://doi.org/10.1016/j.cell.2019.04.011

@article{178e615e5a0944fbb6627063683009cc,

title = "A Site of Vulnerability on the Influenza Virus Hemagglutinin Head Domain Trimer Interface",

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. Antibodies targeting a novel site in the head domain of hemagglutinin afford broad protection against influenza.",

keywords = "B-lymphocytes, antibodies, antibodies, antibody-dependent cell cytotoxicity, antigen-antibody reactions, hemagglutinin glycoproteins, influenza A virus, influenza virus, monoclonal, viral",

author = "Sandhya Bangaru and Shanshan Lang and Michael Schotsaert and Vanderven, {Hillary A.} and Xueyong Zhu and Nurgun Kose and Robin Bombardi and Finn, {Jessica A.} and Kent, {Stephen J.} and Pavlo Gilchuk and Iuliia Gilchuk and Turner, {Hannah L.} and Adolfo Garc{\'i}a-Sastre and Sheng Li and Ward, {Andrew B.} and Wilson, {Ian A.} and Crowe, {James E.}",

note = "Funding Information: We thank Henry Tien from the robotics core in the Wilson laboratory for automated crystal screening and Wenli Yu and Yuanzi Huang in the Wilson laboratory for technical support. We thank Rachel Nargi and Rob Carnahan at Vanderbilt for help with mAb production and sequence analysis and Ryan Irving for help with mouse studies. This work was supported by grants from the NIH U19 AI117905 (to J.E.C.), R56 AI127371 (to I.A.W.), and P01 AI097092 (to A.G.-S.) and NIH contracts HHSN272201400024C (to J.E.C.) and HHSN272201400008C (to A.G.-S.). The project described was supported by CTSA award No. UL1 TR002243 from NCATS. Vanderbilt University Medical Center used the non-clinical and pre-clinical services program offered by the NIAID through Contract No. HHSN27220170041I to determine the in vivo activity of FluA-20 in mouse models of influenza conducted by Dr. Jonna Westover at Utah State University. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIGMS, NCATS, NIAID or NIH. X-ray diffraction data were collected at the Advanced Photon Source beamline 23ID-B (GM/CA CAT) and the Stanford Synchrotron Radiation Lightsource beamline 11-1. GM/CA@APS is funded in whole or in part with federal funds from the NCI (ACB-12002) and the NIGMS (AGM-12006). This research used resources of the Advanced Photon Source, a U.S. DOE Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the U.S. DOE, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research and by the NIH, NIGMS (including P41GM103393). S.B. S. Lang, I.A.W. and J.E.C. conceived and designed the research; S.B. R.B. J.A.F. and J.E.C. isolated, sequenced, and analyzed FluA-20 and its clonally related Abs; S.B. S. Lang, and I.G. performed in vitro profiling of FluA-20 activity; S.B. H.A.V. and S.J.K. determined the ADCC activity; S.B. M.S. P.G. I.G. and A.G.-S. performed mouse studies; S. Lang and X.Z. determined the X-ray structures; S.B. and S. Lang analyzed FluA-20/HA interactions and the epitope; S. Li performed the HDX-MS experiments; H.L.T. and A.B.W. performed and analyzed the EM experiments; S.B, S. Lang, I.A.W. and J.E.C. wrote the manuscript. J.E.C. has served as a consultant for Takeda Vaccines, Sanofi Pasteur, Pfizer, and Novavax; is on the Scientific Advisory Boards of CompuVax and Meissa Vaccines; and is Founder of IDBiologics, Inc. A.G.-S. is inventor of patents owned by the Icahn School of Medicine at Mount Sinai in the field of influenza virus vaccines and Abs. All other authors declare no conflict of interest. Vanderbilt University has applied for a patent related to the FluA-20 Ab. Funding Information: We thank Henry Tien from the robotics core in the Wilson laboratory for automated crystal screening and Wenli Yu and Yuanzi Huang in the Wilson laboratory for technical support. We thank Rachel Nargi and Rob Carnahan at Vanderbilt for help with mAb production and sequence analysis and Ryan Irving for help with mouse studies. This work was supported by grants from the NIH U19 AI117905 (to J.E.C.), R56 AI127371 (to I.A.W.), and P01 AI097092 (to A.G.-S.) and NIH contracts HHSN272201400024C (to J.E.C.) and HHSN272201400008C (to A.G.-S.). The project described was supported by CTSA award No. UL1 TR002243 from NCATS . Vanderbilt University Medical Center used the non-clinical and pre-clinical services program offered by the NIAID through Contract No. HHSN27220170041I to determine the in vivo activity of FluA-20 in mouse models of influenza conducted by Dr. Jonna Westover at Utah State University. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIGMS, NCATS, NIAID or NIH. X-ray diffraction data were collected at the Advanced Photon Source beamline 23ID-B (GM/CA CAT) and the Stanford Synchrotron Radiation Lightsource beamline 11-1. GM/CA@APS is funded in whole or in part with federal funds from the NCI ( ACB-12002 ) and the NIGMS ( AGM-12006 ). This research used resources of the Advanced Photon Source , a U.S. DOE Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357 . Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the U.S. DOE , Office of Science , Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515 . The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research and by the NIH , NIGMS (including P41GM103393 ). Funding Information: We thank Henry Tien from the robotics core in the Wilson laboratory for automated crystal screening and Wenli Yu and Yuanzi Huang in the Wilson laboratory for technical support. We thank Rachel Nargi and Rob Carnahan at Vanderbilt for help with mAb production and sequence analysis and Ryan Irving for help with mouse studies. This work was supported by grants from the NIH U19 AI117905 (to J.E.C.), R56 AI127371 (to I.A.W.), and P01 AI097092 (to A.G.-S.)and NIH contracts HHSN272201400024C (to J.E.C.)and HHSN272201400008C (to A.G.-S.). The project described was supported by CTSA award No. UL1 TR002243 from NCATS. Vanderbilt University Medical Center used the non-clinical and pre-clinical services program offered by the NIAID through Contract No. HHSN27220170041I to determine the in vivo activity of FluA-20 in mouse models of influenza conducted by Dr. Jonna Westover at Utah State University. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIGMS, NCATS, NIAID or NIH. X-ray diffraction data were collected at the Advanced Photon Source beamline 23ID-B (GM/CA CAT)and the Stanford Synchrotron Radiation Lightsource beamline 11-1. GM/CA@APS is funded in whole or in part with federal funds from the NCI (ACB-12002)and the NIGMS (AGM-12006). This research used resources of the Advanced Photon Source, a U.S. DOE Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the U.S. DOE, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research and by the NIH, NIGMS (including P41GM103393). S.B. S. Lang, I.A.W. and J.E.C. conceived and designed the research; S.B. R.B. J.A.F. and J.E.C. isolated, sequenced, and analyzed FluA-20 and its clonally related Abs; S.B. S. Lang, and I.G. performed in vitro profiling of FluA-20 activity; S.B. H.A.V. and S.J.K. determined the ADCC activity; S.B. M.S. P.G. I.G. and A.G.-S. performed mouse studies; S. Lang and X.Z. determined the X-ray structures; S.B. and S. Lang analyzed FluA-20/HA interactions and the epitope; S. Li performed the HDX-MS experiments; H.L.T. and A.B.W. performed and analyzed the EM experiments; S.B, S. Lang, I.A.W. and J.E.C. wrote the manuscript. J.E.C. has served as a consultant for Takeda Vaccines, Sanofi Pasteur, Pfizer, and Novavax; is on the Scientific Advisory Boards of CompuVax and Meissa Vaccines; and is Founder of IDBiologics, Inc. A.G.-S. is inventor of patents owned by the Icahn School of Medicine at Mount Sinai in the field of influenza virus vaccines and Abs. All other authors declare no conflict of interest. Vanderbilt University has applied for a patent related to the FluA-20 Ab. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2019",

month = may,

day = "16",

doi = "10.1016/j.cell.2019.04.011",

language = "English",

volume = "177",

pages = "1136--1152.e18",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "5",

}

Bangaru, S, Lang, S, Schotsaert, M, Vanderven, HA, Zhu, X, Kose, N, Bombardi, R, Finn, JA, Kent, SJ, Gilchuk, P, Gilchuk, I, Turner, HL, García-Sastre, A, Li, S, Ward, AB, Wilson, IA & Crowe, JE 2019, 'A Site of Vulnerability on the Influenza Virus Hemagglutinin Head Domain Trimer Interface', Cell, vol. 177, no. 5, pp. 1136-1152.e18. https://doi.org/10.1016/j.cell.2019.04.011

TY - JOUR

T1 - A Site of Vulnerability on the Influenza Virus Hemagglutinin Head Domain Trimer Interface

AU - Bangaru, Sandhya

AU - Lang, Shanshan

AU - Schotsaert, Michael

AU - Vanderven, Hillary A.

AU - Zhu, Xueyong

AU - Kose, Nurgun

AU - Bombardi, Robin

AU - Finn, Jessica A.

AU - Kent, Stephen J.

AU - Gilchuk, Pavlo

AU - Gilchuk, Iuliia

AU - Turner, Hannah L.

AU - García-Sastre, Adolfo

AU - Li, Sheng

AU - Ward, Andrew B.

AU - Wilson, Ian A.

AU - Crowe, James E.

N1 - Funding Information: We thank Henry Tien from the robotics core in the Wilson laboratory for automated crystal screening and Wenli Yu and Yuanzi Huang in the Wilson laboratory for technical support. We thank Rachel Nargi and Rob Carnahan at Vanderbilt for help with mAb production and sequence analysis and Ryan Irving for help with mouse studies. This work was supported by grants from the NIH U19 AI117905 (to J.E.C.), R56 AI127371 (to I.A.W.), and P01 AI097092 (to A.G.-S.) and NIH contracts HHSN272201400024C (to J.E.C.) and HHSN272201400008C (to A.G.-S.). The project described was supported by CTSA award No. UL1 TR002243 from NCATS. Vanderbilt University Medical Center used the non-clinical and pre-clinical services program offered by the NIAID through Contract No. HHSN27220170041I to determine the in vivo activity of FluA-20 in mouse models of influenza conducted by Dr. Jonna Westover at Utah State University. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIGMS, NCATS, NIAID or NIH. X-ray diffraction data were collected at the Advanced Photon Source beamline 23ID-B (GM/CA CAT) and the Stanford Synchrotron Radiation Lightsource beamline 11-1. GM/CA@APS is funded in whole or in part with federal funds from the NCI (ACB-12002) and the NIGMS (AGM-12006). This research used resources of the Advanced Photon Source, a U.S. DOE Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the U.S. DOE, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research and by the NIH, NIGMS (including P41GM103393). S.B. S. Lang, I.A.W. and J.E.C. conceived and designed the research; S.B. R.B. J.A.F. and J.E.C. isolated, sequenced, and analyzed FluA-20 and its clonally related Abs; S.B. S. Lang, and I.G. performed in vitro profiling of FluA-20 activity; S.B. H.A.V. and S.J.K. determined the ADCC activity; S.B. M.S. P.G. I.G. and A.G.-S. performed mouse studies; S. Lang and X.Z. determined the X-ray structures; S.B. and S. Lang analyzed FluA-20/HA interactions and the epitope; S. Li performed the HDX-MS experiments; H.L.T. and A.B.W. performed and analyzed the EM experiments; S.B, S. Lang, I.A.W. and J.E.C. wrote the manuscript. J.E.C. has served as a consultant for Takeda Vaccines, Sanofi Pasteur, Pfizer, and Novavax; is on the Scientific Advisory Boards of CompuVax and Meissa Vaccines; and is Founder of IDBiologics, Inc. A.G.-S. is inventor of patents owned by the Icahn School of Medicine at Mount Sinai in the field of influenza virus vaccines and Abs. All other authors declare no conflict of interest. Vanderbilt University has applied for a patent related to the FluA-20 Ab. Funding Information: We thank Henry Tien from the robotics core in the Wilson laboratory for automated crystal screening and Wenli Yu and Yuanzi Huang in the Wilson laboratory for technical support. We thank Rachel Nargi and Rob Carnahan at Vanderbilt for help with mAb production and sequence analysis and Ryan Irving for help with mouse studies. This work was supported by grants from the NIH U19 AI117905 (to J.E.C.), R56 AI127371 (to I.A.W.), and P01 AI097092 (to A.G.-S.) and NIH contracts HHSN272201400024C (to J.E.C.) and HHSN272201400008C (to A.G.-S.). The project described was supported by CTSA award No. UL1 TR002243 from NCATS . Vanderbilt University Medical Center used the non-clinical and pre-clinical services program offered by the NIAID through Contract No. HHSN27220170041I to determine the in vivo activity of FluA-20 in mouse models of influenza conducted by Dr. Jonna Westover at Utah State University. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIGMS, NCATS, NIAID or NIH. X-ray diffraction data were collected at the Advanced Photon Source beamline 23ID-B (GM/CA CAT) and the Stanford Synchrotron Radiation Lightsource beamline 11-1. GM/CA@APS is funded in whole or in part with federal funds from the NCI ( ACB-12002 ) and the NIGMS ( AGM-12006 ). This research used resources of the Advanced Photon Source , a U.S. DOE Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357 . Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the U.S. DOE , Office of Science , Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515 . The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research and by the NIH , NIGMS (including P41GM103393 ). Funding Information: We thank Henry Tien from the robotics core in the Wilson laboratory for automated crystal screening and Wenli Yu and Yuanzi Huang in the Wilson laboratory for technical support. We thank Rachel Nargi and Rob Carnahan at Vanderbilt for help with mAb production and sequence analysis and Ryan Irving for help with mouse studies. This work was supported by grants from the NIH U19 AI117905 (to J.E.C.), R56 AI127371 (to I.A.W.), and P01 AI097092 (to A.G.-S.)and NIH contracts HHSN272201400024C (to J.E.C.)and HHSN272201400008C (to A.G.-S.). The project described was supported by CTSA award No. UL1 TR002243 from NCATS. Vanderbilt University Medical Center used the non-clinical and pre-clinical services program offered by the NIAID through Contract No. HHSN27220170041I to determine the in vivo activity of FluA-20 in mouse models of influenza conducted by Dr. Jonna Westover at Utah State University. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIGMS, NCATS, NIAID or NIH. X-ray diffraction data were collected at the Advanced Photon Source beamline 23ID-B (GM/CA CAT)and the Stanford Synchrotron Radiation Lightsource beamline 11-1. GM/CA@APS is funded in whole or in part with federal funds from the NCI (ACB-12002)and the NIGMS (AGM-12006). This research used resources of the Advanced Photon Source, a U.S. DOE Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the U.S. DOE, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research and by the NIH, NIGMS (including P41GM103393). S.B. S. Lang, I.A.W. and J.E.C. conceived and designed the research; S.B. R.B. J.A.F. and J.E.C. isolated, sequenced, and analyzed FluA-20 and its clonally related Abs; S.B. S. Lang, and I.G. performed in vitro profiling of FluA-20 activity; S.B. H.A.V. and S.J.K. determined the ADCC activity; S.B. M.S. P.G. I.G. and A.G.-S. performed mouse studies; S. Lang and X.Z. determined the X-ray structures; S.B. and S. Lang analyzed FluA-20/HA interactions and the epitope; S. Li performed the HDX-MS experiments; H.L.T. and A.B.W. performed and analyzed the EM experiments; S.B, S. Lang, I.A.W. and J.E.C. wrote the manuscript. J.E.C. has served as a consultant for Takeda Vaccines, Sanofi Pasteur, Pfizer, and Novavax; is on the Scientific Advisory Boards of CompuVax and Meissa Vaccines; and is Founder of IDBiologics, Inc. A.G.-S. is inventor of patents owned by the Icahn School of Medicine at Mount Sinai in the field of influenza virus vaccines and Abs. All other authors declare no conflict of interest. Vanderbilt University has applied for a patent related to the FluA-20 Ab. Publisher Copyright: © 2019 Elsevier Inc.

PY - 2019/5/16

Y1 - 2019/5/16

N2 - 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. Antibodies targeting a novel site in the head domain of hemagglutinin afford broad protection against influenza.

AB - 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. Antibodies targeting a novel site in the head domain of hemagglutinin afford broad protection against influenza.

KW - B-lymphocytes

KW - antibodies

KW - antibody-dependent cell cytotoxicity

KW - antigen-antibody reactions

KW - hemagglutinin glycoproteins

KW - influenza A virus

KW - influenza virus

KW - monoclonal

KW - viral

UR - http://www.scopus.com/inward/record.url?scp=85064739641&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2019.04.011

DO - 10.1016/j.cell.2019.04.011

M3 - Article

C2 - 31100268

AN - SCOPUS:85064739641

SN - 0092-8674

VL - 177

SP - 1136-1152.e18

JO - Cell

JF - Cell

IS - 5

ER -

A Site of Vulnerability on the Influenza Virus Hemagglutinin Head Domain Trimer Interface

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Keywords

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