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Structure paper

TitleStructurally convergent antibodies derived from different vaccine strategies target the influenza virus HA anchor epitope with a subset of V3 and V3 genes.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 1268, Year 2025
Publish dateFeb 2, 2025
AuthorsTing-Hui Lin / Chang-Chun David Lee / Monica L Fernández-Quintero / James A Ferguson / Julianna Han / Xueyong Zhu / Wenli Yu / Jenna J Guthmiller / Florian Krammer / Patrick C Wilson / Andrew B Ward / Ian A Wilson /
PubMed AbstractH1N1 influenza viruses are responsible for both seasonal and pandemic influenza. The continual antigenic shift and drift of these viruses highlight the urgent need for a universal influenza vaccine ...H1N1 influenza viruses are responsible for both seasonal and pandemic influenza. The continual antigenic shift and drift of these viruses highlight the urgent need for a universal influenza vaccine to elicit broadly neutralizing antibodies (bnAbs). Identification and characterization of bnAbs elicited in natural infection and immunization to influenza virus hemagglutinin (HA) can provide insights for development of a universal influenza vaccine. Here, we structurally and biophysically characterize four antibodies that bind to a conserved region on the HA membrane-proximal region known as the anchor epitope. Despite some diversity in their V and V genes, the antibodies interact with the HA through germline-encoded residues in HCDR2 and LCDR3. Somatic mutations on HCDR3 also contribute hydrophobic interactions with the conserved HA epitope. This convergent binding mode provides extensive neutralization breadth against H1N1 viruses and suggests possible countermeasures against H1N1 viruses.
External linksNat Commun / PubMed:39894881 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.01 - 3.29 Å
Structure data

46994

9dm0

EMDB-46994, PDB-9dm0:
Cryo-EM structure of the SFV009 3G01 Fab in complex with A/California/04/2009
Method: EM (single particle) / Resolution: 2.9 Å

PDB-9dru:
Crystal structure of 04709_4F04 Fab in complex with H1 HA from A/California/04/2009(H1N1)
Method: X-RAY DIFFRACTION / Resolution: 2.75 Å

PDB-9ds1:
Crystal structure of 241_2F04 Fab in complex with H1 HA from A/California/04/2009(H1N1)
Method: X-RAY DIFFRACTION / Resolution: 2.4 Å

PDB-9ds2:
Crystal structure of 346-54 Fab in complex with H1 HA from A/California/04/2009(H1N1)
Method: X-RAY DIFFRACTION / Resolution: 3.29 Å

PDB-9dsc:
Crystal structure of Apo-241_2F04-A95a mutant Fab
Method: X-RAY DIFFRACTION / Resolution: 2.01 Å

Chemicals

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

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
  • influenza a virus (a/california/04/2009(h1n1))
  • influenza a virus
KeywordsIMMUNE SYSTEM / hemagglutinin / HA / antibody / anchor epitope / influenza virus / VIRAL PROTEIN/IMMUNE SYSTEM / H1N1 / VIRAL PROTEIN-IMMUNE SYSTEM complex / VIRAL PROTEIN

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