File Download
 
Links for fulltext
(May Require Subscription)
 
Supplementary

Article: A highly conserved neutralizing epitope on group 2 influenza A viruses
  • Basic View
  • Metadata View
  • XML View
TitleA highly conserved neutralizing epitope on group 2 influenza A viruses
 
AuthorsEkiert, DC3
Friesen, RHE5
Bhabha, G3
Kwaks, T5
Jongeneelen, M5
Yu, W3
Ophorst, C5
Cox, F5
Korse, HJWM5
Brandenburg, B5
Vogels, R5
Brakenhoff, JPJ5
Kompier, R5 4
Koldijk, MH5
Cornelissen, LAHM2
Poon, LLM1
Peiris, M1
Koudstaal, W5
Wilson, IA3
Goudsmit, J5
 
Issue Date2011
 
PublisherAmerican Association for the Advancement of Science. The Journal's web site is located at http://sciencemag.org
 
CitationScience, 2011, v. 333 n. 6044, p. 843-850 [How to Cite?]
DOI: http://dx.doi.org/10.1126/science.1204839
 
AbstractCurrent flu vaccines provide only limited coverage against seasonal strains of influenza viruses. The identification of VH1-69 antibodies that broadly neutralize almost all influenza A group 1 viruses constituted a breakthrough in the influenza field. Here, we report the isolation and characterization of a human monoclonal antibody CR8020 with broad neutralizing activity against most group 2 viruses, including H3N2 and H7N7, which cause severe human infection. The crystal structure of Fab CR8020 with the 1968 pandemic H3 hemagglutinin (HA) reveals a highly conserved epitope in the HA stalk distinct from the epitope recognized by the VH1-69 group 1 antibodies. Thus, a cocktail of two antibodies may be sufficient to neutralize most influenza A subtypes and, hence, enable development of a universal flu vaccine and broad-spectrum antibody therapies.
 
ISSN0036-8075
2013 Impact Factor: 31.477
2013 SCImago Journal Rankings: 12.465
 
DOIhttp://dx.doi.org/10.1126/science.1204839
 
PubMed Central IDPMC3210727
 
ISI Accession Number IDWOS:000293785400032
Funding AgencyGrant Number
National Institute of Allergy and Infectious Diseases, NIH, Department of Health and Human Services, USAHHSN272200900060C
University Grants Committee, Hong KongAoE/M-12/06
NIHGM080209
Skaggs Institute
DOE Office of Biological and Environmental Research
NIH, National Center for Research Resources
National Institute of General Medical Sciences
Funding Information:

We thank H. Tien and D. Marciano of the Robotics Core at the Joint Center for Structural Genomics for automated crystal screening; T. Doukov and the staff of the SSRL BL9-2 for beamline support; X. Dai and R. Stanfield for excellent assistance with data collection, processing, and analyses; R. Lerner, J. Paulson, and D. Burton for valuable comments and insightful discussion; E. Geelen, D. Spek, and V. Klaren for excellent assistance and advice; K. Hegmans, A. Lourbakos, J. Meijer, and A. Apetri and their teams for producing the mAbs and Fabs; C. Y. H. Leung for providing the A/WF/Hong Kong/MPA892/06 virus; E. de Boer-Luijtze and technicians in the groups of P. van Rossum and S. Riemersma for assistance with the animal experiments; E. Brown from Ottawa University, Canada for the mouse-adapted A/Hong Kong/1/68 strain; and A. Dingemans for critical review of the manuscript. This project has been funded in part by the National Institute of Allergy and Infectious Diseases, NIH, Department of Health and Human Services, USA, under contract HHSN272200900060C; the Area of Excellence Scheme of the University Grants Committee, Hong Kong (grant AoE/M-12/06); a predoctoral fellowship from the Achievement Rewards for College Scientists Foundation (D. C. E.); grant GM080209 from the NIH Molecular Evolution Training Program (D. C. E.); and the Skaggs Institute (I. A. W.). Portions of this research were carried out at the Stanford Synchrotron Radiation Lightsource, a national user facility operated by Stanford University on behalf of the U.S. Department of Energy (DOE), Office of Basic Energy Sciences. The Stanford Synchrotron Radiation Lightsource (SSRL) Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research and by NIH, National Center for Research Resources, Biomedical Technology Program, and the National Institute of General Medical Sciences. This is publication 20951 from the Scripps Research Institute. Coordinates and structure factors have been deposited in the Protein Data Bank (PDB code 3SDY). Nucleotide sequences for the CR8020 variable regions have been deposited in GenBank (accession nos. JN093122, JN093123). A patent application relating to antibody CR8020 has been filed (International Publication Number WO2010/130636). Sharing of materials will be subject to standard material transfer agreements.

 
ReferencesReferences in Scopus
 
GrantsControl of Pandemic and Inter-pandemic Influenza
 
DC FieldValue
dc.contributor.authorEkiert, DC
 
dc.contributor.authorFriesen, RHE
 
dc.contributor.authorBhabha, G
 
dc.contributor.authorKwaks, T
 
dc.contributor.authorJongeneelen, M
 
dc.contributor.authorYu, W
 
dc.contributor.authorOphorst, C
 
dc.contributor.authorCox, F
 
dc.contributor.authorKorse, HJWM
 
dc.contributor.authorBrandenburg, B
 
dc.contributor.authorVogels, R
 
dc.contributor.authorBrakenhoff, JPJ
 
dc.contributor.authorKompier, R
 
dc.contributor.authorKoldijk, MH
 
dc.contributor.authorCornelissen, LAHM
 
dc.contributor.authorPoon, LLM
 
dc.contributor.authorPeiris, M
 
dc.contributor.authorKoudstaal, W
 
dc.contributor.authorWilson, IA
 
dc.contributor.authorGoudsmit, J
 
dc.date.accessioned2011-07-27T01:31:00Z
 
dc.date.available2011-07-27T01:31:00Z
 
dc.date.issued2011
 
dc.description.abstractCurrent flu vaccines provide only limited coverage against seasonal strains of influenza viruses. The identification of VH1-69 antibodies that broadly neutralize almost all influenza A group 1 viruses constituted a breakthrough in the influenza field. Here, we report the isolation and characterization of a human monoclonal antibody CR8020 with broad neutralizing activity against most group 2 viruses, including H3N2 and H7N7, which cause severe human infection. The crystal structure of Fab CR8020 with the 1968 pandemic H3 hemagglutinin (HA) reveals a highly conserved epitope in the HA stalk distinct from the epitope recognized by the VH1-69 group 1 antibodies. Thus, a cocktail of two antibodies may be sufficient to neutralize most influenza A subtypes and, hence, enable development of a universal flu vaccine and broad-spectrum antibody therapies.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationScience, 2011, v. 333 n. 6044, p. 843-850 [How to Cite?]
DOI: http://dx.doi.org/10.1126/science.1204839
 
dc.identifier.citeulike9667792
 
dc.identifier.doihttp://dx.doi.org/10.1126/science.1204839
 
dc.identifier.eissn1095-9203
 
dc.identifier.epage850
 
dc.identifier.hkuros188541
 
dc.identifier.isiWOS:000293785400032
Funding AgencyGrant Number
National Institute of Allergy and Infectious Diseases, NIH, Department of Health and Human Services, USAHHSN272200900060C
University Grants Committee, Hong KongAoE/M-12/06
NIHGM080209
Skaggs Institute
DOE Office of Biological and Environmental Research
NIH, National Center for Research Resources
National Institute of General Medical Sciences
Funding Information:

We thank H. Tien and D. Marciano of the Robotics Core at the Joint Center for Structural Genomics for automated crystal screening; T. Doukov and the staff of the SSRL BL9-2 for beamline support; X. Dai and R. Stanfield for excellent assistance with data collection, processing, and analyses; R. Lerner, J. Paulson, and D. Burton for valuable comments and insightful discussion; E. Geelen, D. Spek, and V. Klaren for excellent assistance and advice; K. Hegmans, A. Lourbakos, J. Meijer, and A. Apetri and their teams for producing the mAbs and Fabs; C. Y. H. Leung for providing the A/WF/Hong Kong/MPA892/06 virus; E. de Boer-Luijtze and technicians in the groups of P. van Rossum and S. Riemersma for assistance with the animal experiments; E. Brown from Ottawa University, Canada for the mouse-adapted A/Hong Kong/1/68 strain; and A. Dingemans for critical review of the manuscript. This project has been funded in part by the National Institute of Allergy and Infectious Diseases, NIH, Department of Health and Human Services, USA, under contract HHSN272200900060C; the Area of Excellence Scheme of the University Grants Committee, Hong Kong (grant AoE/M-12/06); a predoctoral fellowship from the Achievement Rewards for College Scientists Foundation (D. C. E.); grant GM080209 from the NIH Molecular Evolution Training Program (D. C. E.); and the Skaggs Institute (I. A. W.). Portions of this research were carried out at the Stanford Synchrotron Radiation Lightsource, a national user facility operated by Stanford University on behalf of the U.S. Department of Energy (DOE), Office of Basic Energy Sciences. The Stanford Synchrotron Radiation Lightsource (SSRL) Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research and by NIH, National Center for Research Resources, Biomedical Technology Program, and the National Institute of General Medical Sciences. This is publication 20951 from the Scripps Research Institute. Coordinates and structure factors have been deposited in the Protein Data Bank (PDB code 3SDY). Nucleotide sequences for the CR8020 variable regions have been deposited in GenBank (accession nos. JN093122, JN093123). A patent application relating to antibody CR8020 has been filed (International Publication Number WO2010/130636). Sharing of materials will be subject to standard material transfer agreements.

 
dc.identifier.issn0036-8075
2013 Impact Factor: 31.477
2013 SCImago Journal Rankings: 12.465
 
dc.identifier.issue6044
 
dc.identifier.openurl
 
dc.identifier.pmcidPMC3210727
 
dc.identifier.pmid21737702
 
dc.identifier.scopuseid_2-s2.0-80051635697
 
dc.identifier.spage843
 
dc.identifier.urihttp://hdl.handle.net/10722/135274
 
dc.identifier.volume333
 
dc.languageeng
 
dc.publisherAmerican Association for the Advancement of Science. The Journal's web site is located at http://sciencemag.org
 
dc.publisher.placeUnited States
 
dc.relation.ispartofScience
 
dc.relation.projectControl of Pandemic and Inter-pandemic Influenza
 
dc.relation.referencesReferences in Scopus
 
dc.rightsScience. Copyright © American Association for the Advancement of Science.
 
dc.subject.meshAntibodies, Monoclonal - immunology - isolation and purification
 
dc.subject.meshAntibodies, Neutralizing - immunology - isolation and purification
 
dc.subject.meshAntibodies, Viral - immunology - isolation and purification
 
dc.subject.meshAntigens, Viral - chemistry - genetics - immunology
 
dc.subject.meshHemagglutinin Glycoproteins, Influenza Virus - chemistry - genetics - immunology
 
dc.titleA highly conserved neutralizing epitope on group 2 influenza A viruses
 
dc.typeArticle
 
<?xml encoding="utf-8" version="1.0"?>
<item><contributor.author>Ekiert, DC</contributor.author>
<contributor.author>Friesen, RHE</contributor.author>
<contributor.author>Bhabha, G</contributor.author>
<contributor.author>Kwaks, T</contributor.author>
<contributor.author>Jongeneelen, M</contributor.author>
<contributor.author>Yu, W</contributor.author>
<contributor.author>Ophorst, C</contributor.author>
<contributor.author>Cox, F</contributor.author>
<contributor.author>Korse, HJWM</contributor.author>
<contributor.author>Brandenburg, B</contributor.author>
<contributor.author>Vogels, R</contributor.author>
<contributor.author>Brakenhoff, JPJ</contributor.author>
<contributor.author>Kompier, R</contributor.author>
<contributor.author>Koldijk, MH</contributor.author>
<contributor.author>Cornelissen, LAHM</contributor.author>
<contributor.author>Poon, LLM</contributor.author>
<contributor.author>Peiris, M</contributor.author>
<contributor.author>Koudstaal, W</contributor.author>
<contributor.author>Wilson, IA</contributor.author>
<contributor.author>Goudsmit, J</contributor.author>
<date.accessioned>2011-07-27T01:31:00Z</date.accessioned>
<date.available>2011-07-27T01:31:00Z</date.available>
<date.issued>2011</date.issued>
<identifier.citation>Science, 2011, v. 333 n. 6044, p. 843-850</identifier.citation>
<identifier.issn>0036-8075</identifier.issn>
<identifier.uri>http://hdl.handle.net/10722/135274</identifier.uri>
<description.abstract>Current flu vaccines provide only limited coverage against seasonal strains of influenza viruses. The identification of VH1-69 antibodies that broadly neutralize almost all influenza A group 1 viruses constituted a breakthrough in the influenza field. Here, we report the isolation and characterization of a human monoclonal antibody CR8020 with broad neutralizing activity against most group 2 viruses, including H3N2 and H7N7, which cause severe human infection. The crystal structure of Fab CR8020 with the 1968 pandemic H3 hemagglutinin (HA) reveals a highly conserved epitope in the HA stalk distinct from the epitope recognized by the VH1-69 group 1 antibodies. Thus, a cocktail of two antibodies may be sufficient to neutralize most influenza A subtypes and, hence, enable development of a universal flu vaccine and broad-spectrum antibody therapies.</description.abstract>
<language>eng</language>
<publisher>American Association for the Advancement of Science. The Journal&apos;s web site is located at http://sciencemag.org</publisher>
<relation.ispartof>Science</relation.ispartof>
<rights>Science. Copyright &#169; American Association for the Advancement of Science.</rights>
<subject.mesh>Antibodies, Monoclonal - immunology - isolation and purification</subject.mesh>
<subject.mesh>Antibodies, Neutralizing - immunology - isolation and purification</subject.mesh>
<subject.mesh>Antibodies, Viral - immunology - isolation and purification</subject.mesh>
<subject.mesh>Antigens, Viral - chemistry - genetics - immunology</subject.mesh>
<subject.mesh>Hemagglutinin Glycoproteins, Influenza Virus - chemistry - genetics - immunology</subject.mesh>
<title>A highly conserved neutralizing epitope on group 2 influenza A viruses</title>
<type>Article</type>
<identifier.openurl>http://library.hku.hk:4550/resserv?sid=HKU:IR&amp;issn=0036-8075&amp;volume=333&amp;issue=6044&amp;spage=843&amp;epage=850&amp;date=2011&amp;atitle=A+highly+conserved+neutralizing+epitope+on+group+2+influenza+A+viruses</identifier.openurl>
<description.nature>link_to_subscribed_fulltext</description.nature>
<identifier.doi>10.1126/science.1204839</identifier.doi>
<identifier.pmid>21737702</identifier.pmid>
<identifier.pmcid>PMC3210727</identifier.pmcid>
<identifier.scopus>eid_2-s2.0-80051635697</identifier.scopus>
<identifier.hkuros>188541</identifier.hkuros>
<relation.references>http://www.scopus.com/mlt/select.url?eid=2-s2.0-80051635697&amp;selection=ref&amp;src=s&amp;origin=recordpage</relation.references>
<identifier.volume>333</identifier.volume>
<identifier.issue>6044</identifier.issue>
<identifier.spage>843</identifier.spage>
<identifier.epage>850</identifier.epage>
<identifier.eissn>1095-9203</identifier.eissn>
<identifier.isi>WOS:000293785400032</identifier.isi>
<publisher.place>United States</publisher.place>
<relation.project>Control of Pandemic and Inter-pandemic Influenza</relation.project>
<identifier.citeulike>9667792</identifier.citeulike>
</item>
Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. Wageningen University and Research Centre
  3. Scripps Research Institute
  4. FluConsult
  5. Crucell NV