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Structure paper

TitleHighly conserved protective epitopes on influenza B viruses.
Journal, issue, pagesScience, Vol. 337, Issue 6100, Page 1343-1348, Year 2012
Publish dateSep 14, 2012
AuthorsCyrille Dreyfus / Nick S Laursen / Ted Kwaks / David Zuijdgeest / Reza Khayat / Damian C Ekiert / Jeong Hyun Lee / Zoltan Metlagel / Miriam V Bujny / Mandy Jongeneelen / Remko van der Vlugt / Mohammed Lamrani / Hans J W M Korse / Eric Geelen / Özcan Sahin / Martijn Sieuwerts / Just P J Brakenhoff / Ronald Vogels / Olive T W Li / Leo L M Poon / Malik Peiris / Wouter Koudstaal / Andrew B Ward / Ian A Wilson / Jaap Goudsmit / Robert H E Friesen /
PubMed AbstractIdentification of broadly neutralizing antibodies against influenza A viruses has raised hopes for the development of monoclonal antibody-based immunotherapy and "universal" vaccines for influenza. ...Identification of broadly neutralizing antibodies against influenza A viruses has raised hopes for the development of monoclonal antibody-based immunotherapy and "universal" vaccines for influenza. However, a substantial part of the annual flu burden is caused by two cocirculating, antigenically distinct lineages of influenza B viruses. Here, we report human monoclonal antibodies, CR8033, CR8071, and CR9114, that protect mice against lethal challenge from both lineages. Antibodies CR8033 and CR8071 recognize distinct conserved epitopes in the head region of the influenza B hemagglutinin (HA), whereas CR9114 binds a conserved epitope in the HA stem and protects against lethal challenge with influenza A and B viruses. These antibodies may inform on development of monoclonal antibody-based treatments and a universal flu vaccine for all influenza A and B viruses.
External linksScience / PubMed:22878502 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.71 - 19.0 Å
Structure data

EMDB-2143:
Highly Conserved Protective Epitopes on Influenza B Viruses
Method: EM (single particle) / Resolution: 15.0 Å

EMDB-2144:
Highly Conserved Protective Epitopes on Influenza B Viruses
Method: EM (single particle) / Resolution: 17.0 Å

EMDB-2145:
Electron microscopy of Influenza hemagglutinin (Malaysia/2506/2004) in complex with neutralizing antibody (Fab CR8071
Method: EM (single particle) / Resolution: 19.0 Å

EMDB-2146:
Electron microscopy of Influenza hemagglutinin (Malaysia/2506/2004) in complex with neutralizing antibody (Fab CR9114
Method: EM (single particle) / Resolution: 18.0 Å

EMDB-2147:
Electron microscopy of Influenza hemagglutinin (South Carolina/1/1918 (H1N1)) in complex with neutralizing antibody (Fab CR9114)
Method: EM (single particle) / Resolution: 18.0 Å

EMDB-2148:
Electron microscopy of Influenza hemagglutinin (Hong Kong/1/1968 (H3N2)) in complex with neutralizing antibody (Fab CR9114)
Method: EM (single particle) / Resolution: 17.0 Å

EMDB-2149:
Electron microscopy of Influenza hemagglutinin (Wisconsin/1/1966 (H9N2)) in complex with neutralizing antibody (Fab CR9114)
Method: EM (single particle) / Resolution: 14.8 Å

EMDB-2150:
Electron microscopy of Influenza hemagglutinin (Netherlands/219/2003 (H7N7)) in complex with neutralizing antibody (Fab CR9114)
Method: EM (single particle) / Resolution: 17.5 Å

PDB-4fqh:
Crystal Structure of Fab CR9114
Method: X-RAY DIFFRACTION / Resolution: 2.05 Å

PDB-4fqi:
Crystal Structure of Fab CR9114 in Complex with a H5N1 influenza virus hemagglutinin
Method: X-RAY DIFFRACTION / Resolution: 1.71 Å

PDB-4fqj:
Influenza B/Florida/4/2006 hemagglutinin Fab CR8071 complex
Method: X-RAY DIFFRACTION / Resolution: 2.5 Å

PDB-4fqk:
Influenza B/Brisbane/60/2008 hemagglutinin Fab CR8059 complex
Method: X-RAY DIFFRACTION / Resolution: 5.65 Å

PDB-4fql:
Influenza B HA Antibody (Fab) CR8033
Method: X-RAY DIFFRACTION / Resolution: 1.898 Å

PDB-4fqm:
Structure of B/Brisbane/60/2008 Influenza Hemagglutinin
Method: X-RAY DIFFRACTION / Resolution: 3.45 Å

PDB-4fqv:
Crystal structure of broadly neutralizing antibody CR9114 bound to H7 influenza hemagglutinin
Method: X-RAY DIFFRACTION / Resolution: 5.75 Å

PDB-4fqy:
Crystal structure of broadly neutralizing antibody CR9114 bound to H3 influenza hemagglutinin
Method: X-RAY DIFFRACTION / Resolution: 5.253 Å

Chemicals

ChemComp-EDO:
1,2-ETHANEDIOL / Ethylene glycol

ChemComp-NO3:
NITRATE ION / Nitrate

ChemComp-HOH:
WATER / Water

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-GOL:
GLYCEROL / Glycerol

Source
  • Influenza B virus (B/Florida/4/2006)
  • homo sapiens (human)
  • Influenza B virus (B/Malaysia/2506/2004)
  • Influenza A virus (A/South Carolina/1/1918(H1N1))
  • Influenza A virus (A/Hong Kong/1/1968(H3N2))
  • Influenza A virus (A/turkey/Wisconsin/1/1966(H9N2))
  • Influenza A virus (A/Netherlands/219/2003(H7N7))
  • influenza a virus
  • influenza b virus
KeywordsIMMUNE SYSTEM / neutralizing antibodies / antibody affinity / antigens / epitope / glycosylation / hemagglutinin glycoproteins / immunoglobulin Fab fragment / influenza virus / influenza vaccines / membrane fusion / VIRAL PROTEIN/IMMUNE SYSTEM / epitopes / immunoglobulin Fab fragments / H5N1 subtype / avian flu / envelope protein / VIRAL PROTEIN-IMMUNE SYSTEM complex / monoclonal / immunoglobulin / antibody / Fab fragment / viral / Influenza B virus / VIRAL PROTEIN / Hemagglutinin / viral fusion protein / virus attachment and entry / immune recognition

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