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Structure paper

TitleUniversal protection against influenza infection by a multidomain antibody to influenza hemagglutinin.
Journal, issue, pagesScience, Vol. 362, Issue 6414, Page 598-602, Year 2018
Publish dateNov 2, 2018
AuthorsNick S Laursen / Robert H E Friesen / Xueyong Zhu / Mandy Jongeneelen / Sven Blokland / Jan Vermond / Alida van Eijgen / Chan Tang / Harry van Diepen / Galina Obmolova / Marijn van der Neut Kolfschoten / David Zuijdgeest / Roel Straetemans / Ryan M B Hoffman / Travis Nieusma / Jesper Pallesen / Hannah L Turner / Steffen M Bernard / Andrew B Ward / Jinquan Luo / Leo L M Poon / Anna P Tretiakova / James M Wilson / Maria P Limberis / Ronald Vogels / Boerries Brandenburg / Joost A Kolkman / Ian A Wilson /
PubMed AbstractBroadly neutralizing antibodies against highly variable pathogens have stimulated the design of vaccines and therapeutics. We report the use of diverse camelid single-domain antibodies to influenza ...Broadly neutralizing antibodies against highly variable pathogens have stimulated the design of vaccines and therapeutics. We report the use of diverse camelid single-domain antibodies to influenza virus hemagglutinin to generate multidomain antibodies with impressive breadth and potency. Multidomain antibody MD3606 protects mice against influenza A and B infection when administered intravenously or expressed locally from a recombinant adeno-associated virus vector. Crystal and single-particle electron microscopy structures of these antibodies with hemagglutinins from influenza A and B viruses reveal binding to highly conserved epitopes. Collectively, our findings demonstrate that multidomain antibodies targeting multiple epitopes exhibit enhanced virus cross-reactivity and potency. In combination with adeno-associated virus-mediated gene delivery, they may provide an effective strategy to prevent infection with influenza virus and other highly variable pathogens.
External linksScience / PubMed:30385580 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution0.92 - 6.9 Å
Structure data

EMDB-9029:
Hemagglutinin trimeric ectodomain (B/Massachusetts/02/2012) in complex with Fab from IgG CR9114 and single-domain antibody SD84
Method: EM (single particle) / Resolution: 6.9 Å

PDB-6ck8:
Crystal structure of anti-influenza single-domain llama antibody SD38
Method: X-RAY DIFFRACTION / Resolution: 2.05 Å

PDB-6cnv:
INFLUENZA B/BRISBANE HEMAGGLUTININ FAB CR9115 SD84H COMPLEX
Method: X-RAY DIFFRACTION / Resolution: 4.1 Å

PDB-6cnw:
STRUCTURE OF HUMANIZED SINGLE DOMAIN ANTIBODY SD84
Method: X-RAY DIFFRACTION / Resolution: 0.92 Å

PDB-6fys:
Structure of single domain antibody SD83
Method: X-RAY DIFFRACTION / Resolution: 2 Å

PDB-6fyt:
Structure of H1 (A/solomon Islands/3/06) Influenza Hemagglutinin in complex with SD38
Method: X-RAY DIFFRACTION / Resolution: 2.8 Å

PDB-6fyu:
Structure of H7(A/Shanghai/2/2013) Influenza Hemagglutinin in complex SD36
Method: X-RAY DIFFRACTION / Resolution: 2.643 Å

PDB-6fyw:
Structure of B/Brisbane/60/2008 Influenza Hemagglutinin in complex with SD83
Method: X-RAY DIFFRACTION / Resolution: 2.2 Å

Chemicals

ChemComp-SO4:
SULFATE ION

ChemComp-1PE:
PENTAETHYLENE GLYCOL / precipitant*YM

ChemComp-GOL:
GLYCEROL

ChemComp-HOH:
WATER

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-ACT:
ACETATE ION

ChemComp-PEG:
DI(HYDROXYETHYL)ETHER

ChemComp-EDO:
1,2-ETHANEDIOL

ChemComp-NA:
Unknown entry

Source
  • Influenza B virus (B/Massachusetts/02/2012)
  • homo sapiens (human)
  • lama glama (llama)
  • influenza b virus
  • human immunodeficiency virus 1
  • synthetic construct (others)
  • hybrid (others)
  • influenza a virus (a/solomon islands/3/2006(h1n1))
  • influenza a virus
  • influenza b virus (b/brisbane/60/2008)
KeywordsIMMUNE SYSTEM / single-domain / multi-domain / llama / antibody / influenza / broad / neutralization / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex / Single domain antibody / hemagglutinin / humanization

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