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Article: A highly conserved neutralizing epitope on group 2 influenza A viruses

TitleA highly conserved neutralizing epitope on group 2 influenza A viruses
Authors
Issue Date2011
PublisherAmerican Association for the Advancement of Science. The Journal's web site is located at http://sciencemag.org
Citation
Science, 2011, v. 333 n. 6044, p. 843-850 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/135274
ISSN
2014 Impact Factor: 33.611
2014 SCImago Journal Rankings: 10.107
PubMed Central ID
ISI Accession Number ID
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.

References
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DC FieldValueLanguage
dc.contributor.authorEkiert, DCen_HK
dc.contributor.authorFriesen, RHEen_HK
dc.contributor.authorBhabha, Gen_HK
dc.contributor.authorKwaks, Ten_HK
dc.contributor.authorJongeneelen, Men_HK
dc.contributor.authorYu, Wen_HK
dc.contributor.authorOphorst, Cen_HK
dc.contributor.authorCox, Fen_HK
dc.contributor.authorKorse, HJWMen_HK
dc.contributor.authorBrandenburg, Ben_HK
dc.contributor.authorVogels, Ren_HK
dc.contributor.authorBrakenhoff, JPJen_HK
dc.contributor.authorKompier, Ren_HK
dc.contributor.authorKoldijk, MHen_HK
dc.contributor.authorCornelissen, LAHMen_HK
dc.contributor.authorPoon, LLMen_HK
dc.contributor.authorPeiris, Men_HK
dc.contributor.authorKoudstaal, Wen_HK
dc.contributor.authorWilson, IAen_HK
dc.contributor.authorGoudsmit, Jen_HK
dc.date.accessioned2011-07-27T01:31:00Z-
dc.date.available2011-07-27T01:31:00Z-
dc.date.issued2011en_HK
dc.identifier.citationScience, 2011, v. 333 n. 6044, p. 843-850en_HK
dc.identifier.issn0036-8075en_HK
dc.identifier.urihttp://hdl.handle.net/10722/135274-
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.en_HK
dc.languageengen_US
dc.publisherAmerican Association for the Advancement of Science. The Journal's web site is located at http://sciencemag.orgen_HK
dc.relation.ispartofScienceen_HK
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 virusesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0036-8075&volume=333&issue=6044&spage=843&epage=850&date=2011&atitle=A+highly+conserved+neutralizing+epitope+on+group+2+influenza+A+viruses-
dc.identifier.emailPoon, LLM: llmpoon@hkucc.hku.hken_HK
dc.identifier.emailPeiris, M: malik@hkucc.hku.hken_HK
dc.identifier.authorityPoon, LLM=rp00484en_HK
dc.identifier.authorityPeiris, M=rp00410en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1126/science.1204839en_HK
dc.identifier.pmid21737702en_HK
dc.identifier.pmcidPMC3210727-
dc.identifier.scopuseid_2-s2.0-80051635697en_HK
dc.identifier.hkuros188541en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80051635697&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume333en_HK
dc.identifier.issue6044en_HK
dc.identifier.spage843en_HK
dc.identifier.epage850en_HK
dc.identifier.eissn1095-9203-
dc.identifier.isiWOS:000293785400032-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectControl of Pandemic and Inter-pandemic Influenza-
dc.identifier.scopusauthoridEkiert, DC=6504355759en_HK
dc.identifier.scopusauthoridFriesen, RHE=26648237000en_HK
dc.identifier.scopusauthoridBhabha, G=23007791000en_HK
dc.identifier.scopusauthoridKwaks, T=6505918270en_HK
dc.identifier.scopusauthoridJongeneelen, M=8609959300en_HK
dc.identifier.scopusauthoridYu, W=24170367300en_HK
dc.identifier.scopusauthoridOphorst, C=6507859865en_HK
dc.identifier.scopusauthoridCox, F=8679913700en_HK
dc.identifier.scopusauthoridKorse, HJWM=49861388800en_HK
dc.identifier.scopusauthoridBrandenburg, B=8541161900en_HK
dc.identifier.scopusauthoridVogels, R=7005841896en_HK
dc.identifier.scopusauthoridBrakenhoff, JPJ=55406091200en_HK
dc.identifier.scopusauthoridKompier, R=6507495028en_HK
dc.identifier.scopusauthoridKoldijk, MH=15739781600en_HK
dc.identifier.scopusauthoridCornelissen, LAHM=6506562393en_HK
dc.identifier.scopusauthoridPoon, LLM=7005441747en_HK
dc.identifier.scopusauthoridPeiris, M=7005486823en_HK
dc.identifier.scopusauthoridKoudstaal, W=6508125014en_HK
dc.identifier.scopusauthoridWilson, IA=34574375200en_HK
dc.identifier.scopusauthoridGoudsmit, J=35374719700en_HK
dc.identifier.citeulike9667792-

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